Wild-type p53 controls the level of fibronectin expression in breast cancer cells

You,Daeun; Jung,Seung  Pil; Jeong,Yisun; Bae,Soo  Youn; Kim,Sangmin

doi:10.3892/or.2017.5860

Wild-type p53 controls the level of fibronectin expression in breast cancer cells

Authors:
- Daeun You
- Seung Pil Jung
- Yisun Jeong
- Soo Youn Bae
- Sangmin Kim
View Affiliations

Affiliations: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Gangnam-gu, Seoul 06351, Republic of Korea, Division of Breast and Endocrine Surgery, Department of Surgery, Korea University Hospital, Korea University College of Medicine, Seongbuk-gu, Seoul 02852, Republic of Korea, Department of Breast Cancer Center, Samsung Medical Center, Gangnam-gu, Seoul 06351, Republic of Korea
Published online on: July 31, 2017 https://doi.org/10.3892/or.2017.5860
Pages: 2551-2557

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Aberrant fibronectin (FN) expression is associated with poor prognosis, cell adhesion, and cell motility in a variety of cancer cells. In this study, we investigated the relationship between p53 and FN expression in breast cancer cells. Basal FN expression was significantly decreased by treatment with the p53 activator III, RITA, in MCF7 breast cancer cells with wild-type p53. In addition, overexpression of wild-type p53 markedly decreased the level of FN expression in p53-mutant breast cancer cells. To examine the mechanism underlying the relationship between p53 and FN expression, we treated MCF7 breast cancer cells with the tumor promoter TPA (12-O-tetradecanoylphorbol-13-acetate). Our results showed that basal FN expression was increased by TPA treatment in a time-dependent manner. In contrast, the level of p53 expression was decreased by TPA treatment. However, the expression of FN and p53 was not altered by TPA in p53-mutant breast cancer cells. Furthermore, the alterations in FN and p53 expression in response to TPA were prevented by a specific MEK inhibitor, UO126. Finally, we demonstrated that TPA triggers degradation of p53 through the proteasomal pathway in MCF7 cells. TPA-induced FN expression was decreased by the proteasome inhibitor MG132. Under the same condition, p53 protein expression, but not mRNA expression, was reversed by MG132. Taken together, our data demonstrate that the level of FN expression is associated with the status and expression of p53 in breast cancer cells.

View Figures

View References

1	Kornblihtt AR and Gutman A: Molecular biology of the extracellular matrix proteins. Biol Rev Camb Philos Soc. 63:465–507. 1988. View Article : Google Scholar : PubMed/NCBI
2	Balanis N, Wendt MK, Schiemann BJ, Wang Z, Schiemann WP and Carlin CR: Epithelial to mesenchymal transition promotes breast cancer progression via a fibronectin-dependent STAT3 signaling pathway. J Biol Chem. 288:17954–17967. 2013. View Article : Google Scholar : PubMed/NCBI
3	Guan JL: Role of focal adhesion kinase in integrin signaling. Int J Biochem Cell Biol. 29:1085–1096. 1997. View Article : Google Scholar : PubMed/NCBI
4	Qian P, Zuo Z, Wu Z, Meng X, Li G, Wu Z, Zhang W, Tan S, Pandey V, Yao Y, et al: Pivotal role of reduced let-7g expression in breast cancer invasion and metastasis. Cancer Res. 71:6463–6474. 2011. View Article : Google Scholar : PubMed/NCBI
5	Jeon M, Lee J, Nam SJ, Shin I, Lee JE and Kim S: Induction of fibronectin by HER2 overexpression triggers adhesion and invasion of breast cancer cells. Exp Cell Res. 333:116–126. 2015. View Article : Google Scholar : PubMed/NCBI
6	Fernandez-Garcia B, Eiró N, Marín L, González-Reyes S, González LO, Lamelas ML and Vizoso FJ: Expression and prognostic significance of fibronectin and matrix metalloproteases in breast cancer metastasis. Histopathology. 64:512–522. 2014. View Article : Google Scholar : PubMed/NCBI
7	Bae YK, Kim A, Kim MK, Choi JE, Kang SH and Lee SJ: Fibronectin expression in carcinoma cells correlates with tumor aggressiveness and poor clinical outcome in patients with invasive breast cancer. Hum Pathol. 44:2028–2037. 2013. View Article : Google Scholar : PubMed/NCBI
8	Woods DB and Vousden KH: Regulation of p53 function. Exp Cell Res. 264:56–66. 2001. View Article : Google Scholar : PubMed/NCBI
9	Sugrue MM, Shin DY, Lee SW and Aaronson SA: Wild-type p53 triggers a rapid senescence program in human tumor cells lacking functional p53. Proc Natl Acad Sci USA. 94:9648–9653. 1997. View Article : Google Scholar : PubMed/NCBI
10	Royds JA and Iacopetta B: p53 and disease: When the guardian angel fails. Cell Death Differ. 13:1017–1026. 2006. View Article : Google Scholar : PubMed/NCBI
11	Sur S, Pagliarini R, Bunz F, Rago C, Diaz LA Jr, Kinzler KW, Vogelstein B and Papadopoulos N: A panel of isogenic human cancer cells suggests a therapeutic approach for cancers with inactivated p53. Proc Natl Acad Sci USA. 106:3964–3969. 2009. View Article : Google Scholar : PubMed/NCBI
12	Petitjean A, Mathe E, Kato S, Ishioka C, Tavtigian SV, Hainaut P and Olivier M: Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: Lessons from recent developments in the IARC TP53 database. Hum Mutat. 28:622–629. 2007. View Article : Google Scholar : PubMed/NCBI
13	Di Agostino S, Strano S, Emiliozzi V, Zerbini V, Mottolese M, Sacchi A, Blandino G and Piaggio G: Gain of function of mutant p53: The mutant p53/NF-Y protein complex reveals an aberrant transcriptional mechanism of cell cycle regulation. Cancer Cell. 10:191–202. 2006. View Article : Google Scholar : PubMed/NCBI
14	Abbas T, White D, Hui L, Yoshida K, Foster DA and Bargonetti J: Inhibition of human p53 basal transcription by down-regulation of protein kinase Cdelta. J Biol Chem. 279:9970–9977. 2004. View Article : Google Scholar : PubMed/NCBI
15	Nam JM, Onodera Y, Bissell MJ and Park CC: Breast cancer cells in three-dimensional culture display an enhanced radioresponse after coordinate targeting of integrin alpha5beta1 and fibronectin. Cancer Res. 70:5238–5248. 2010. View Article : Google Scholar : PubMed/NCBI
16	Huang L, Cheng HC, Isom R, Chen CS, Levine RA and Pauli BU: Protein kinase Cepsilon mediates polymeric fibronectin assembly on the surface of blood-borne rat breast cancer cells to promote pulmonary metastasis. J Biol Chem. 283:7616–7627. 2008. View Article : Google Scholar : PubMed/NCBI
17	Mitra AK, Sawada K, Tiwari P, Mui K, Gwin K and Lengyel E: Ligand-independent activation of c-Met by fibronectin and α(5)β(1)-integrin regulates ovarian cancer invasion and metastasis. Oncogene. 30:1566–1576. 2011. View Article : Google Scholar : PubMed/NCBI
18	Pontiggia O, Sampayo R, Raffo D, Motter A, Xu R, Bissell MJ, Joffé EB and Simian M: The tumor microenvironment modulates tamoxifen resistance in breast cancer: A role for soluble stromal factors and fibronectin through β1 integrin. Breast Cancer Res Treat. 133:459–471. 2012. View Article : Google Scholar : PubMed/NCBI
19	Levine AJ: p53, the cellular gatekeeper for growth and division. Cell. 88:323–331. 1997. View Article : Google Scholar : PubMed/NCBI
20	Issaeva N, Bozko P, Enge M, Protopopova M, Verhoef LG, Masucci M, Pramanik A and Selivanova G: Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nat Med. 10:1321–1328. 2004. View Article : Google Scholar : PubMed/NCBI
21	Espinoza-Fonseca LM: Targeting MDM2 by the small molecule RITA: Towards the development of new multi-target drugs against cancer. Theor Biol Med Model. 2:382005. View Article : Google Scholar : PubMed/NCBI
22	Enge M, Bao W, Hedström E, Jackson SP, Moumen A and Selivanova G: MDM2-dependent downregulation of p21 and hnRNP K provides a switch between apoptosis and growth arrest induced by pharmacologically activated p53. Cancer Cell. 15:171–183. 2009. View Article : Google Scholar : PubMed/NCBI
23	Grinkevich VV, Nikulenkov F, Shi Y, Enge M, Bao W, Maljukova A, Gluch A, Kel A, Sangfelt O and Selivanova G: Ablation of key oncogenic pathways by RITA-reactivated p53 is required for efficient apoptosis. Cancer Cell. 15:441–453. 2009. View Article : Google Scholar : PubMed/NCBI
24	Zhao CY, Grinkevich VV, Nikulenkov F, Bao W and Selivanova G: Rescue of the apoptotic-inducing function of mutant p53 by small molecule RITA. Cell Cycle. 9:1847–1855. 2010. View Article : Google Scholar : PubMed/NCBI
25	Oh SJ, Jung SP, Han J, Kim S, Kim JS, Nam SJ, Lee JE and Kim JH: Silibinin inhibits TPA-induced cell migration and MMP-9 expression in thyroid and breast cancer cells. Oncol Rep. 29:1343–1348. 2013. View Article : Google Scholar : PubMed/NCBI
26	Yoon JH, Choi YJ and Lee SG: Ginsenoside Rh1 suppresses matrix metalloproteinase-1 expression through inhibition of activator protein-1 and mitogen-activated protein kinase signaling pathway in human hepatocellular carcinoma cells. Eur J Pharmacol. 679:24–33. 2012. View Article : Google Scholar : PubMed/NCBI
27	Kikkawa U, Takai Y, Tanaka Y, Miyake R and Nishizuka Y: Protein kinase C as a possible receptor protein of tumor-promoting phorbol esters. J Biol Chem. 258:11442–11445. 1983.PubMed/NCBI
28	Robbins D, Ponville J, Morris K and Zhao Y: Involvement of PTEN in TPA-mediated p53-activation in mouse skin epidermal JB6 cells. FEBS Lett. 586:4108–4113. 2012. View Article : Google Scholar : PubMed/NCBI
29	Ashcroft M, Taya Y and Vousden KH: Stress signals utilize multiple pathways to stabilize p53. Mol Cell Biol. 20:3224–3233. 2000. View Article : Google Scholar : PubMed/NCBI