Role of TGFβ in regulation of the tumor microenvironment and drug delivery (Review)
- Authors:
- Panagiotis Papageorgis
- Triantafyllos Stylianopoulos
-
Affiliations: Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia 1678, Cyprus - Published online on: January 7, 2015 https://doi.org/10.3892/ijo.2015.2816
- Pages: 933-943
-
Copyright: © Papageorgis et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
This article is mentioned in:
Abstract
 |
 |
|
Derynck R and Akhurst RJ: Differentiation plasticity regulated by TGF-beta family proteins in development and disease. Nat Cell Biol. 9:1000–1004. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Wakefield LM and Hill CS: Beyond TGFβ: roles of other TGFβ superfamily members in cancer. Nat Rev Cancer. 13:328–341. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Massagué J, Seoane J and Wotton D: Smad transcription factors. Genes Dev. 19:2783–2810. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Annes JP, Munger JS and Rifkin DB: Making sense of latent TGFbeta activation. J Cell Sci. 116:217–224. 2003. View Article : Google Scholar | |
|
Gleizes PE, Beavis RC, Mazzieri R, Shen B and Rifkin DB: Identification and characterization of an eight-cysteine repeat of the latent transforming growth factor-beta binding protein-1 that mediates bonding to the latent transforming growth factor-beta1. J Biol Chem. 271:29891–29896. 1996. View Article : Google Scholar : PubMed/NCBI | |
|
Miyazono K, Olofsson A, Colosetti P and Heldin CH: A role of the latent TGF-beta 1-binding protein in the assembly and secretion of TGF-beta 1. EMBO J. 10:1091–1101. 1991.PubMed/NCBI | |
|
Saharinen J, Taipale J and Keski-Oja J: Association of the small latent transforming growth factor-beta with an eight cysteine repeat of its binding protein LTBP-1. EMBO J. 15:245–253. 1996.PubMed/NCBI | |
|
Unsöld C, Hyytiäinen M, Bruckner-Tuderman L and Keski-Oja J: Latent TGF-beta binding protein LTBP-1 contains three potential extracellular matrix interacting domains. J Cell Sci. 114:187–197. 2001. | |
|
Nunes I, Gleizes PE, Metz CN and Rifkin DB: Latent transforming growth factor-beta binding protein domains involved in activation and transglutaminase-dependent cross-linking of latent transforming growth factor-beta. J Cell Biol. 136:1151–1163. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Lawrence DA, Pircher R, Krycève-Martinerie C and Jullien P: Normal embryo fibroblasts release transforming growth factors in a latent form. J Cell Physiol. 121:184–188. 1984. View Article : Google Scholar : PubMed/NCBI | |
|
Crawford SE, Stellmach V, Murphy-Ullrich JE, et al: Thrombospondin-1 is a major activator of TGF-beta1 in vivo. Cell. 93:1159–1170. 1998. View Article : Google Scholar : PubMed/NCBI | |
|
Ribeiro SM, Poczatek M, Schultz-Cherry S, Villain M and Murphy-Ullrich JE: The activation sequence of thrombos-pondin-1 interacts with the latency-associated peptide to regulate activation of latent transforming growth factor-beta. J Biol Chem. 274:13586–13593. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Dubois CM, Laprise MH, Blanchette F, Gentry LE and Leduc R: Processing of transforming growth factor beta 1 precursor by human furin convertase. J Biol Chem. 270:10618–10624. 1995. View Article : Google Scholar : PubMed/NCBI | |
|
Sato Y and Rifkin DB: Inhibition of endothelial cell movement by pericytes and smooth muscle cells: activation of a latent transforming growth factor-beta 1-like molecule by plasmin during co-culture. J Cell Biol. 109:309–315. 1989. View Article : Google Scholar : PubMed/NCBI | |
|
Yu Q and Stamenkovic I: Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev. 14:163–176. 2000.PubMed/NCBI | |
|
Derynck R, Zhang Y and Feng XH: Smads: transcriptional activators of TGF-beta responses. Cell. 95:737–740. 1998. View Article : Google Scholar : PubMed/NCBI | |
|
Massagué J: TGF-beta signal transduction. Annu Rev Biochem. 67:753–791. 1998. View Article : Google Scholar : PubMed/NCBI | |
|
Riggins GJ, Thiagalingam S, Rozenblum E, et al: Mad-related genes in the human. Nat Genet. 13:347–349. 1996. View Article : Google Scholar : PubMed/NCBI | |
|
Lagna G, Hata A, Hemmati-Brivanlou A and Massagué J: Partnership between DPC4 and SMAD proteins in TGF-beta signalling pathways. Nature. 383:832–836. 1996. View Article : Google Scholar : PubMed/NCBI | |
|
Nakao A, Imamura T, Souchelnytskyi S, et al: TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4. EMBO J. 16:5353–5362. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Heldin CH, Miyazono K and ten Dijke P: TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature. 390:465–471. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Bierie B and Moses HL: Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer. Nat Rev Cancer. 6:506–520. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Lewis KA, Gray PC, Blount AL, et al: Betaglycan binds inhibin and can mediate functional antagonism of activin signalling. Nature. 404:411–414. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Wrana JL, Attisano L, Wieser R, Ventura F and Massagué J: Mechanism of activation of the TGF-beta receptor. Nature. 370:341–347. 1994. View Article : Google Scholar : PubMed/NCBI | |
|
Shi Y and Massagué J: Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell. 113:685–700. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Miyazono K, Maeda S and Imamura T: BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev. 16:251–263. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Derynck R and Zhang YE: Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 425:577–584. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Abdollah S, Macías-Silva M, Tsukazaki T, Hayashi H, Attisano L and Wrana JL: TbetaRI phosphorylation of Smad2 on Ser465 and Ser467 is required for Smad2-Smad4 complex formation and signaling. J Biol Chem. 272:27678–27685. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang Y, Feng X, We R and Derynck R: Receptor-associated Mad homologues synergize as effectors of the TGF-beta response. Nature. 383:168–172. 1996. View Article : Google Scholar : PubMed/NCBI | |
|
Tsukazaki T, Chiang TA, Davison AF, Attisano L and Wrana JL: SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor. Cell. 95:779–791. 1998. View Article : Google Scholar : PubMed/NCBI | |
|
Feng XH, Zhang Y, Wu RY and Derynck R: The tumor suppressor Smad4/DPC4 and transcriptional adaptor CBP/p300 are coactivators for smad3 in TGF-beta-induced transcriptional activation. Genes Dev. 12:2153–2163. 1998. View Article : Google Scholar : PubMed/NCBI | |
|
Janknecht R, Wells NJ and Hunter T: TGF-beta-stimulated cooperation of smad proteins with the coactivators CBP/p300. Genes Dev. 12:2114–2119. 1998. View Article : Google Scholar : PubMed/NCBI | |
|
Itoh S, Ericsson J, Nishikawa J, Heldin CH and ten Dijke P: The transcriptional co-activator P/CAF potentiates TGF-beta/Smad signaling. Nucleic Acids Res. 28:4291–4298. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Bai RY, Koester C, Ouyang T, et al: SMIF, a Smad4-interacting protein that functions as a co-activator in TGFbeta signalling. Nat Cell Biol. 4:181–190. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Chen CR, Kang Y, Siegel PM and Massagué J: E2F4/5 and p107 as Smad cofactors linking the TGFbeta receptor to c-myc repression. Cell. 110:19–32. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Kang Y, Chen CR and Massagué J: A self-enabling TGFbeta response coupled to stress signaling: Smad engages stress response factor ATF3 for Id1 repression in epithelial cells. Mol Cell. 11:915–926. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Wotton D, Knoepfler PS, Laherty CD, Eisenman RN and Massagué J: The Smad transcriptional corepressor TGIF recruits mSin3. Cell Growth Differ. 12:457–463. 2001.PubMed/NCBI | |
|
Akiyoshi S, Inoue H, Hanai J, et al: c-Ski acts as a transcriptional co-repressor in transforming growth factor-beta signaling through interaction with smads. J Biol Chem. 274:35269–35277. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Luo K, Stroschein SL, Wang W, et al: The Ski oncoprotein interacts with the Smad proteins to repress TGFbeta signaling. Genes Dev. 13:2196–2206. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Stroschein SL, Wang W, Zhou S, Zhou Q and Luo K: Negative feedback regulation of TGF-beta signaling by the SnoN onco-protein. Science. 286:771–774. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Sun Y, Liu X, Eaton EN, Lane WS, Lodish HF and Weinberg RA: Interaction of the Ski oncoprotein with Smad3 regulates TGF-beta signaling. Mol Cell. 4:499–509. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Seoane J, Le HV, Shen L, Anderson SA and Massagué J: Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell. 117:211–223. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Pardali K, Kurisaki A, Morén A, ten Dijke P, Kardassis D and Moustakas A: Role of Smad proteins and transcription factor Sp1 in p21(Waf1/Cip1) regulation by transforming growth factor-beta. J Biol Chem. 275:29244–29256. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang Y, Feng XH and Derynck R: Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription. Nature. 394:909–913. 1998. View Article : Google Scholar : PubMed/NCBI | |
|
Lin X, Liang YY, Sun B, et al: Smad6 recruits transcription corepressor CtBP to repress bone morphogenetic protein-induced transcription. Mol Cell Biol. 23:9081–9093. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Peng Y, Zhao S, Song L, Wang M and Jiao K: Sertad1 encodes a novel transcriptional co-activator of SMAD1 in mouse embryonic hearts. Biochem Biophys Res Commun. 441:751–756. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Izutsu K, Kurokawa M, Imai Y, Maki K, Mitani K and Hirai H: The corepressor CtBP interacts with Evi-1 to repress transforming growth factor beta signaling. Blood. 97:2815–2822. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Xi Q, Wang Z, Zaromytidou AI, et al: A poised chromatin platform for TGF-β access to master regulators. Cell. 147:1511–1524. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Ross S, Cheung E, Petrakis TG, Howell M, Kraus WL and Hill CS: Smads orchestrate specific histone modifications and chromatin remodeling to activate transcription. EMBO J. 25:4490–4502. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Papageorgis P, Lambert AW, Ozturk S, et al: Smad signaling is required to maintain epigenetic silencing during breast cancer progression. Cancer Res. 70:968–978. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Nakao A, Afrakhte M, Morén A, et al: Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature. 389:631–635. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Itóh S, Landström M, Hermansson A, et al: Transforming growth factor beta1 induces nuclear export of inhibitory Smad7. J Biol Chem. 273:29195–29201. 1998. View Article : Google Scholar : PubMed/NCBI | |
|
Hayashi H, Abdollah S, Qiu Y, et al: The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling. Cell. 89:1165–1173. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Ebisawa T, Fukuchi M, Murakami G, et al: Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation. J Biol Chem. 276:12477–12480. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Kavsak P, Rasmussen RK, Causing CG, et al: Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation. Mol Cell. 6:1365–1375. 2000. View Article : Google Scholar | |
|
Zhang S, Fei T, Zhang L, et al: Smad7 antagonizes transforming growth factor beta signaling in the nucleus by interfering with functional Smad-DNA complex formation. Mol Cell Biol. 27:4488–4499. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang YE: Non-Smad pathways in TGF-beta signaling. Cell Res. 19:128–139. 2009. View Article : Google Scholar : | |
|
Hartsough MT and Mulder KM: Transforming growth factor beta activation of p44mapk in proliferating cultures of epithelial cells. J Biol Chem. 270:7117–7124. 1995. View Article : Google Scholar : PubMed/NCBI | |
|
Frey RS and Mulder KM: TGFbeta regulation of mitogen-activated protein kinases in human breast cancer cells. Cancer Lett. 117:41–50. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Papageorgis P, Cheng K, Ozturk S, et al: Smad4 inactivation promotes malignancy and drug resistance of colon cancer. Cancer Res. 71:998–1008. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Finlay GA, Thannickal VJ, Fanburg BL and Paulson KE: Transforming growth factor-beta 1-induced activation of the ERK pathway/activator protein-1 in human lung fibroblasts requires the autocrine induction of basic fibroblast growth factor. J Biol Chem. 275:27650–27656. 2000.PubMed/NCBI | |
|
Vinals F and Pouysségur J: Transforming growth factor beta1 (TGF-beta1) promotes endothelial cell survival during in vitro angiogenesis via an autocrine mechanism implicating TGF-alpha signaling. Mol Cell Biol. 21:7218–7230. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Ellenrieder V, Hendler SF, Boeck W, et al: Transforming growth factor beta1 treatment leads to an epithelial-mesenchymal transdifferentiation of pancreatic cancer cells requiring extra-cellular signal-regulated kinase 2 activation. Cancer Res. 61:4222–4228. 2001.PubMed/NCBI | |
|
Xie L, Law BK, Chytil AM, Brown KA, Aakre ME and Moses HL: Activation of the Erk pathway is required for TGF-beta1-induced EMT in vitro. Neoplasia. 6:603–610. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Lee MK, Pardoux C, Hall MC, et al: TGF-beta activates Erk MAP kinase signalling through direct phosphorylation of ShcA. EMBO J. 26:3957–3967. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Liao JH, Chen JS, Chai MQ, Zhao S and Song JG: The involvement of p38 MAPK in transforming growth factor beta1-induced apoptosis in murine hepatocytes. Cell Res. 11:89–94. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Kimura N, Matsuo R, Shibuya H, Nakashima K and Taga T: BMP2-induced apoptosis is mediated by activation of the TAK1-p38 kinase pathway that is negatively regulated by Smad6. J Biol Chem. 275:17647–17652. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Bakin AV, Rinehart C, Tomlinson AK and Arteaga CL: p38 mitogen-activated protein kinase is required for TGFbeta-mediated fibroblastic transdifferentiation and cell migration. J Cell Sci. 115:3193–3206. 2002.PubMed/NCBI | |
|
Hocevar BA, Brown TL and Howe PH: TGF-beta induces fibronectin synthesis through a c-Jun N-terminal kinase-dependent, Smad4-independent pathway. EMBO J. 18:1345–1356. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Yu L, Hébert MC and Zhang YE: TGF-beta receptor-activated p38 MAP kinase mediates Smad-independent TGF-beta responses. EMBO J. 21:3749–3759. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Yamaguchi K, Shirakabe K, Shibuya H, et al: Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction. Science. 270:2008–2011. 1995. View Article : Google Scholar : PubMed/NCBI | |
|
Shim JH, Xiao C, Paschal AE, et al: TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo. Genes Dev. 19:2668–2681. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Sorrentino A, Thakur N, Grimsby S, et al: The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner. Nat Cell Biol. 10:1199–1207. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Yamashita M, Fatyol K, Jin C, Wang X, Liu Z and Zhang YE: TRAF6 mediates Smad-independent activation of JNK and p38 by TGF-beta. Mol Cell. 31:918–924. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang L, Wang W, Hayashi Y, et al: A role for MEK kinase 1 in TGF-beta/activin-induced epithelium movement and embryonic eyelid closure. EMBO J. 22:4443–4454. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Kim KY, Kim BC, Xu Z and Kim SJ: Mixed lineage kinase 3 (MLK3)-activated p38 MAP kinase mediates transforming growth factor-beta-induced apoptosis in hepatoma cells. J Biol Chem. 279:29478–29484. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Jaffe AB and Hall A: Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol. 21:247–269. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Bhowmick NA, Ghiassi M, Bakin A, et al: Transforming growth factor-beta1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism. Mol Biol Cell. 12:27–36. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Edlund S, Landström M, Heldin CH and Aspenström P: Transforming growth factor-beta-induced mobilization of actin cytoskeleton requires signaling by small GTPases Cdc42 and RhoA. Mol Biol Cell. 13:902–914. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Ozdamar B, Bose R, Barrios-Rodiles M, Wang HR, Zhang Y and Wrana JL: Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity. Science. 307:1603–1609. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Bakin AV, Tomlinson AK, Bhowmick NA, Moses HL and Arteaga CL: Phosphatidylinositol 3-kinase function is required for transforming growth factor beta-mediated epithelial to mesenchymal transition and cell migration. J Biol Chem. 275:36803–36810. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Shin I, Bakin AV, Rodeck U, Brunet A and Arteaga CL: Transforming growth factor beta enhances epithelial cell survival via Akt-dependent regulation of FKHRL1. Mol Biol Cell. 12:3328–3339. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Hidalgo M and Rowinsky EK: The rapamycin-sensitive signal transduction pathway as a target for cancer therapy. Oncogene. 19:6680–6686. 2000. View Article : Google Scholar | |
|
Lamouille S and Derynck R: Cell size and invasion in TGF-beta-induced epithelial to mesenchymal transition is regulated by activation of the mTOR pathway. J Cell Biol. 178:437–451. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Roberts AB and Wakefield LM: The two faces of transforming growth factor beta in carcinogenesis. Proc Natl Acad Sci USA. 100:8621–8623. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Tang B, Vu M, Booker T, et al: TGF-beta switches from tumor suppressor to prometastatic factor in a model of breast cancer progression. J Clin Invest. 112:1116–1124. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Wakefield LM and Roberts AB: TGF-beta signaling: positive and negative effects on tumorigenesis. Curr Opin Genet Dev. 12:22–29. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Siegel PM, Shu W, Cardiff RD, Muller WJ and Massagué J: Transforming growth factor beta signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary metastasis. Proc Natl Acad Sci USA. 100:8430–8435. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Siegel PM and Massagué J: Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat Rev Cancer. 3:807–821. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Choi ME and Ballermann BJ: Inhibition of capillary morphogenesis and associated apoptosis by dominant negative mutant transforming growth factor-beta receptors. J Biol Chem. 270:21144–21150. 1995. View Article : Google Scholar : PubMed/NCBI | |
|
Hyman KM, Seghezzi G, Pintucci G, et al: Transforming growth factor-beta1 induces apoptosis in vascular endothelial cells by activation of mitogen-activated protein kinase. Surgery. 132:173–179. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Rich JN, Zhang M, Datto MB, Bigner DD and Wang XF: Transforming growth factor-beta-mediated p15(INK4B) induction and growth inhibition in astrocytes is SMAD3-dependent and a pathway prominently altered in human glioma cell lines. J Biol Chem. 274:35053–35058. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Yang X, Letterio JJ, Lechleider RJ, et al: Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-beta. EMBO J. 18:1280–1291. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Laiho M, DeCaprio JA, Ludlow JW, Livingston DM and Massagué J: Growth inhibition by TGF-beta linked to suppression of retinoblastoma protein phosphorylation. Cell. 62:175–185. 1990. View Article : Google Scholar : PubMed/NCBI | |
|
Hannon GJ and Beach D: p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest. Nature. 371:257–261. 1994. View Article : Google Scholar : PubMed/NCBI | |
|
Datto MB, Li Y, Panus JF, Howe DJ, Xiong Y and Wang XF: Transforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism. Proc Natl Acad Sci USA. 92:5545–5549. 1995. View Article : Google Scholar : PubMed/NCBI | |
|
Polyak K, Kato JY, Solomon MJ, et al: p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest. Genes Dev. 8:9–22. 1994. View Article : Google Scholar : PubMed/NCBI | |
|
Pietenpol JA, Stein RW, Moran E, et al: TGF-beta 1 inhibition of c-myc transcription and growth in keratinocytes is abrogated by viral transforming proteins with pRB binding domains. Cell. 61:777–785. 1990. View Article : Google Scholar : PubMed/NCBI | |
|
Norton JD: ID helix-loop-helix proteins in cell growth, differentiation and tumorigenesis. J Cell Sci. 113:3897–3905. 2000.PubMed/NCBI | |
|
Grotendorst GR: Connective tissue growth factor: a mediator of TGF-beta action on fibroblasts. Cytokine Growth Factor Rev. 8:171–179. 1997. View Article : Google Scholar | |
|
Park K, Kim SJ, Bang YJ, et al: Genetic changes in the transforming growth factor beta (TGF-beta) type II receptor gene in human gastric cancer cells: correlation with sensitivity to growth inhibition by TGF-beta. Proc Natl Acad Sci USA. 91:8772–8776. 1994. View Article : Google Scholar : PubMed/NCBI | |
|
Kim IY, Ahn HJ, Zelner DJ, et al: Genetic change in transforming growth factor beta (TGF-beta) receptor type I gene correlates with insensitivity to TGF-beta 1 in human prostate cancer cells. Cancer Res. 56:44–48. 1996.PubMed/NCBI | |
|
Markowitz S, Wang J, Myeroff L, et al: Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science. 268:1336–1338. 1995. View Article : Google Scholar : PubMed/NCBI | |
|
Riggins GJ, Kinzler KW, Vogelstein B and Thiagalingam S: Frequency of Smad gene mutations in human cancers. Cancer Res. 57:2578–2580. 1997.PubMed/NCBI | |
|
Schutte M, Hruban RH, Hedrick L, et al: DPC4 gene in various tumor types. Cancer Res. 56:2527–2530. 1996.PubMed/NCBI | |
|
Eppert K, Scherer SW, Ozcelik H, et al: MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma. Cell. 86:543–552. 1996. View Article : Google Scholar : PubMed/NCBI | |
|
Hahn SA, Hoque AT, Moskaluk CA, et al: Homozygous deletion map at 18q21.1 in pancreatic cancer. Cancer Res. 56:490–494. 1996.PubMed/NCBI | |
|
Hahn SA, Schutte M, Hoque AT, et al: DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science. 271:350–353. 1996. View Article : Google Scholar : PubMed/NCBI | |
|
Thiagalingam S, Lengauer C, Leach FS, et al: Evaluation of candidate tumour suppressor genes on chromosome 18 in colorectal cancers. Nat Genet. 13:343–346. 1996. View Article : Google Scholar : PubMed/NCBI | |
|
Schwarte-Waldhoff I, Volpert OV, Bouck NP, et al: Smad4/DPC4-mediated tumor suppression through suppression of angiogenesis. Proc Natl Acad Sci USA. 97:9624–9629. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Kretzschmar M, Doody J, Timokhina I and Massagué J: A mechanism of repression of TGFbeta/Smad signaling by oncogenic Ras. Genes Dev. 13:804–816. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Kretzschmar M, Doody J and Massagué J: Opposing BMP and EGF signalling pathways converge on the TGF-beta family mediator Smad1. Nature. 389:618–622. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Massagué J: Integration of Smad and MAPK pathways: a link and a linker revisited. Genes Dev. 17:2993–2997. 2003. View Article : Google Scholar | |
|
Gomis RR, Alarcón C, Nadal C, Van Poznak C and Massagué J: C/EBPbeta at the core of the TGFbeta cytostatic response and its evasion in metastatic breast cancer cells. Cancer Cell. 10:203–214. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Padua D, Zhang XH, Wang Q, et al: TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4. Cell. 133:66–77. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Thiery JP: Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2:442–454. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Yang J, Mani SA, Donaher JL, et al: Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 117:927–939. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Xu J, Lamouille S and Derynck R: TGF-beta-induced epithelial to mesenchymal transition. Cell Res. 19:156–172. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Cano A, Pérez-Moreno MA, Rodrigo I, et al: The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2:76–83. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Savagner P, Yamada KM and Thiery JP: The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelial-mesenchymal transition. J Cell Biol. 137:1403–1419. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Eger A, Aigner K, Sonderegger S, et al: DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells. Oncogene. 24:2375–2385. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Comijn J, Berx G, Vermassen P, et al: The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell. 7:1267–1278. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Thuault S, Valcourt U, Petersen M, Manfioletti G, Heldin CH and Moustakas A: Transforming growth factor-beta employs HMGA2 to elicit epithelial-mesenchymal transition. J Cell Biol. 174:175–183. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Mani SA, Yang J, Brooks M, et al: Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. Proc Natl Acad Sci USA. 104:10069–10074. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Derynck R, Akhurst RJ and Balmain A: TGF-beta signaling in tumor suppression and cancer progression. Nat Genet. 29:117–129. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Yang J and Weinberg RA: Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell. 14:818–829. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Zhu B, Fukada K, Zhu H and Kyprianou N: Prohibitin and cofilin are intracellular effectors of transforming growth factor beta signaling in human prostate cancer cells. Cancer Res. 66:8640–8647. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Deckers M, van Dinther M, Buijs J, et al: The tumor suppressor Smad4 is required for transforming growth factor beta-induced epithelial to mesenchymal transition and bone metastasis of breast cancer cells. Cancer Res. 66:2202–2209. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Kang Y and Massagué J: Epithelial-mesenchymal transitions: twist in development and metastasis. Cell. 118:277–279. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Grande JP: Role of transforming growth factor-beta in tissue injury and repair. Proc Soc Exp Biol Med. 214:27–40. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Singer AJ and Clark RA: Cutaneous wound healing. N Engl J Med. 341:738–746. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Pickup M, Novitskiy S and Moses HL: The roles of TGFβ in the tumour microenvironment. Nat Rev Cancer. 13:788–799. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Dalal BI, Keown PA and Greenberg AH: Immunocytochemical localization of secreted transforming growth factor-beta 1 to the advancing edges of primary tumors and to lymph node metastases of human mammary carcinoma. Am J Pathol. 143:381–389. 1993.PubMed/NCBI | |
|
Kingsley LA, Fournier PG, Chirgwin JM and Guise TA: Molecular biology of bone metastasis. Mol Cancer Ther. 6:2609–2617. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Prud’homme GJ: Pathobiology of transforming growth factor beta in cancer, fibrosis and immunologic disease, and therapeutic considerations. Lab Invest. 87:1077–1091. 2007. View Article : Google Scholar | |
|
Wrzesinski SH, Wan YY and Flavell RA: Transforming growth factor-beta and the immune response: implications for anti-cancer therapy. Clin Cancer Res. 13:5262–5270. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Akhurst RJ and Hata A: Targeting the TGFβ signalling pathway in disease. Nat Rev Drug Discov. 11:790–811. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Flavell RA, Sanjabi S, Wrzesinski SH and Licona-Limón P: The polarization of immune cells in the tumour environment by TGFbeta. Nat Rev Immunol. 10:554–567. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Laouar Y, Sutterwala FS, Gorelik L and Flavell RA: Transforming growth factor-beta controls T helper type 1 cell development through regulation of natural killer cell interferon-gamma. Nat Immunol. 6:600–607. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Rubtsov YP and Rudensky AY: TGFbeta signalling in control of T-cell-mediated self-reactivity. Nat Rev Immunol. 7:443–453. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Mantovani A, Sozzani S, Locati M, Allavena P and Sica A: Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 23:549–555. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Gong D, Shi W, Yi SJ, Chen H, Groffen J and Heisterkamp N: TGFβ signaling plays a critical role in promoting alternative macrophage activation. BMC Immunol. 13:312012. View Article : Google Scholar | |
|
Fridlender ZG, Sun J, Kim S, et al: Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell. 16:183–194. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Yamaguchi Y, Tsumura H, Miwa M and Inaba K: Contrasting effects of TGF-beta 1 and TNF-alpha on the development of dendritic cells from progenitors in mouse bone marrow. Stem Cells. 15:144–153. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Ramesh S, Wildey GM and Howe PH: Transforming growth factor beta (TGFbeta)-induced apoptosis: the rise & fall of Bim. Cell Cycle. 8:11–17. 2009. View Article : Google Scholar | |
|
Marcoe JP, Lim JR, Schaubert KL, et al: TGF-β is responsible for NK cell immaturity during ontogeny and increased susceptibility to infection during mouse infancy. Nat Immunol. 13:843–850. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Wipff PJ, Rifkin DB, Meister JJ and Hinz B: Myofibroblast contraction activates latent TGF-beta1 from the extracellular matrix. J Cell Biol. 179:1311–1323. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Wipff PJ and Hinz B: Myofibroblasts work best under stress. J Bodyw Mov Ther. 13:121–127. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C and Brown RA: Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol. 3:349–363. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Karagiannis GS, Poutahidis T, Erdman SE, Kirsch R, Riddell RH and Diamandis EP: Cancer-associated fibroblasts drive the progression of metastasis through both paracrine and mechanical pressure on cancer tissue. Mol Cancer Res. 10:1403–1418. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Paszek MJ, Zahir N, Johnson KR, et al: Tensional homeostasis and the malignant phenotype. Cancer Cell. 8:241–254. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Samuel MS, Lopez JI, McGhee EJ, et al: Actomyosin-mediated cellular tension drives increased tissue stiffness and β-catenin activation to induce epidermal hyperplasia and tumor growth. Cancer Cell. 19:776–791. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Branton MH and Kopp JB: TGF-beta and fibrosis. Microbes Infect. 1:1349–1365. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Egeblad M, Rasch MG and Weaver VM: Dynamic interplay between the collagen scaffold and tumor evolution. Curr Opin Cell Biol. 22:697–706. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Smith NR, Baker D, Farren M, et al: Tumor stromal architecture can define the intrinsic tumor response to VEGF-targeted therapy. Clin Cancer Res. 19:6943–6956. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Stylianopoulos T and Jain RK: Combining two strategies to improve perfusion and drug delivery in solid tumors. Proc Natl Acad Sci USA. 110:18632–18637. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Stylianopoulos T, Martin JD, Chauhan VP, et al: Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors. Proc Natl Acad Sci USA. 109:15101–15108. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Demou ZN: Gene expression profiles in 3D tumor analogs indicate compressive strain differentially enhances metastatic potential. Ann Biomed Eng. 38:3509–3520. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Tse JM, Cheng G, Tyrrell JA, et al: Mechanical compression drives cancer cells toward invasive phenotype. Proc Natl Acad Sci USA. 109:911–916. 2012. View Article : Google Scholar : | |
|
Chauhan VP, Martin JD, Liu H, et al: Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumor blood vessels. Nat Commun. 4:25162013. View Article : Google Scholar | |
|
Facciabene A, Peng X, Hagemann IS, et al: Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells. Nature. 475:226–230. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Wilson WR and Hay MP: Targeting hypoxia in cancer therapy. Nat Rev Cancer. 11:393–410. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Jain RK, Martin JD and Stylianopoulos T: The role of mechanical forces in tumor growth and therapy. Annu Rev Biomed Eng. 16:321–346. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Jain RK and Stylianopoulos T: Delivering nanomedicine to solid tumors. Nat Rev Clin Oncol. 7:653–664. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Chauhan VP and Jain RK: Strategies for advancing cancer nanomedicine. Nat Mater. 12:958–962. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Popovi Z, Liu W, Chauhan VP, et al: A nanoparticle size series for in vivo fluorescence imaging. Angew Chem Int Ed Engl. 49:8649–8652. 2010. View Article : Google Scholar | |
|
Stylianopoulos T, Poh MZ, Insin N, et al: Diffusion of particles in the extracellular matrix: the effect of repulsive electrostatic interactions. Biophys J. 99:1342–1349. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Zhong Z, Carroll KD, Policarpio D, et al: Anti-transforming growth factor beta receptor II antibody has therapeutic efficacy against primary tumor growth and metastasis through multi-effects on cancer, stroma, and immune cells. Clin Cancer Res. 16:1191–1205. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Uhl M, Aulwurm S, Wischhusen J, et al: SD-208, a novel transforming growth factor beta receptor I kinase inhibitor, inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in vitro and in vivo. Cancer Res. 64:7954–7961. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Kim S, Buchlis G, Fridlender ZG, et al: Systemic blockade of transforming growth factor-beta signaling augments the efficacy of immunogene therapy. Cancer Res. 68:10247–10256. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Chakrabarti R, Subramaniam V, Abdalla S, Jothy S and Prud’homme GJ: Tranilast inhibits the growth and metastasis of mammary carcinoma. Anticancer Drugs. 20:334–345. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Achyut BR, Bader DA, Robles AI, et al: Inflammation-mediated genetic and epigenetic alterations drive cancer development in the neighboring epithelium upon stromal abrogation of TGF-β signaling. PLoS Genet. 9:e10032512013. View Article : Google Scholar | |
|
Bragado P, Estrada Y, Parikh F, et al: TGF-β2 dictates disseminated tumour cell fate in target organs through TGF-β-RIII and p38α/β signalling. Nat Cell Biol. 15:1351–1361. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Biswas T, Gu X, Yang J, Ellies LG and Sun LZ: Attenuation of TGF-β signaling supports tumor progression of a mesenchymal-like mammary tumor cell line in a syngeneic murine model. Cancer Lett. 346:129–138. 2014. View Article : Google Scholar | |
|
Stockmann C, Doedens A, Weidemann A, et al: Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis. Nature. 456:814–818. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Rhim AD, Mirek ET, Aiello NM, et al: EMT and dissemination precede pancreatic tumor formation. Cell. 148:349–361. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Diop-Frimpong B, Chauhan VP, Krane S, Boucher Y and Jain RK: Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors. Proc Natl Acad Sci USA. 108:2909–2914. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Wilop S, von Hobe S, Crysandt M, Esser A, Osieka R and Jost E: Impact of angiotensin I converting enzyme inhibitors and angiotensin II type 1 receptor blockers on survival in patients with advanced non-small-cell lung cancer undergoing first-line platinum-based chemotherapy. J Cancer Res Clin Oncol. 135:1429–1435. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Keizman D, Huang P, Eisenberger MA, et al: Angiotensin system inhibitors and outcome of sunitinib treatment in patients with metastatic renal cell carcinoma: a retrospective examination. Eur J Cancer. 47:1955–1961. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Nakai Y, Isayama H, Ijichi H, et al: Phase I trial of gemcitabine and candesartan combination therapy in normotensive patients with advanced pancreatic cancer: GECA1. Cancer Sci. 103:1489–1492. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Liu J, Liao S, Diop-Frimpong B, et al: TGF-β blockade improves the distribution and efficacy of therapeutics in breast carcinoma by normalizing the tumor stroma. Proc Natl Acad Sci USA. 109:16618–16623. 2012. View Article : Google Scholar | |
|
Kozono S, Ohuchida K, Eguchi D, et al: Pirfenidone inhibits pancreatic cancer desmoplasia by regulating stellate cells. Cancer Res. 73:2345–2356. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Bouquet F, Pal A, Pilones KA, et al: TGFβ1 inhibition increases the radiosensitivity of breast cancer cells in vitro and promotes tumor control by radiation in vivo. Clin Cancer Res. 17:6754–6765. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang M, Kleber S, Röhrich M, et al: Blockade of TGF-β signaling by the TGFβR-I kinase inhibitor LY2109761 enhances radiation response and prolongs survival in glioblastoma. Cancer Res. 71:7155–7167. 2011. View Article : Google Scholar : PubMed/NCBI |
