LIM homeobox transcription factors, a novel subfamily which plays an important role in cancer (Review)
- Authors:
- Xi Wang
- Chao He
- Xiaotong Hu
-
Affiliations: Biomedical Research Center, Sir Run Run Shaw Hospital, Zhejiang University and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, Zhejiang 310016, P.R. China - Published online on: March 27, 2014 https://doi.org/10.3892/or.2014.3112
- Pages: 1975-1985
This article is mentioned in:
Abstract
![]() |
![]() |
![]() |
Hobert O and Westphal H: Functions of LIM-homeobox genes. Trends Genet. 16:75–83. 2000. View Article : Google Scholar : PubMed/NCBI | |
Dawid IB: LIM domain proteins. C R Acad Sci. 3:295–306. 1995. | |
Bach I: The LIM domain: regulation by association. Mech Dev. 91:5–17. 2000. View Article : Google Scholar : PubMed/NCBI | |
Glenn DJ and Maurer RA: MRG1 binds to the LIM domain of Lhx2 and may function as a coactivator to stimulate glycoprotein hormone alpha-subunit gene expression. J Biol Chem. 274:36159–36167. 1999. View Article : Google Scholar : PubMed/NCBI | |
Howard PW and Maurer RA: Identification of a conserved protein that interacts with specific LIM homeodomain transcription factors. J Biol Chem. 275:13336–13342. 2000. View Article : Google Scholar : PubMed/NCBI | |
Ostendorff HP, Peirano RI, Peters MA, et al: Ubiquitination-dependent cofactor exchange on LIM homeodomain transcription factors. Nature. 416:99–103. 2002. View Article : Google Scholar : PubMed/NCBI | |
Shawlot W and Behringer RR: Requirement for Lim1 in head-organizer function. Nature. 374:425–430. 1995. View Article : Google Scholar : PubMed/NCBI | |
Karavanov AA, Karavanova I, Perantoni A and Dawid IB: Expression pattern of the rat Lim-1 homeobox gene suggests a dual role during kidney development. Int J Dev Biol. 42:61–66. 1998.PubMed/NCBI | |
Kobayashi A, Kwan KM, Carroll TJ, McMahon AP, Mendelsohn CL and Behringer RR: Distinct and sequential tissue-specific activities of the LIM-class homeobox gene Lim1 for tubular morphogenesis during kidney development. Development. 132:2809–2823. 2005. View Article : Google Scholar : PubMed/NCBI | |
Chen YT, Kobayashi A, Kwan KM, Johnson RL and Behringer RR: Gene expression profiles in developing nephrons using Lim1 metanephric mesenchyme-specific conditional mutant mice. BMC Nephrol. 7:12006. View Article : Google Scholar : PubMed/NCBI | |
Guertl B, Senanayake U, Nusshold E, et al: Lim1, an embryonal transcription factor, is absent in multicystic renal dysplasia, but reactivated in nephroblastomas. Pathobiology. 78:210–219. 2011. View Article : Google Scholar : PubMed/NCBI | |
Dormoy V, Béraud C, Lindner V, Thomas L, Coquard C, Barthelmebs M, Jacqmin D, Lang H and Massfelder T: LIM-class homeobox gene Lim1, a novel oncogene in human renal cell carcinoma. Oncogene. 30:1753–1763. 2011. View Article : Google Scholar : PubMed/NCBI | |
Xu Y, Baldassare M, Fisher P, et al: LH-2: a LIM/homeodomain gene expressed in developing lymphocytes and neural cells. Proc Natl Acad Sci USA. 90:227–231. 1993. View Article : Google Scholar : PubMed/NCBI | |
Richter K, Pinto do OP, Hägglund AC, Wahlin A and Carlsson L: Lhx2 expression in hematopoietic progenitor/stem cells in vivo causes a chronic myeloproliferative disorder and altered globin expression. Haematologica. 88:1336–1347. 2003.PubMed/NCBI | |
Nadal N, Chapiro E, Flandrin-Gresta P, et al: LHX2 deregulation by juxtaposition with the IGH locus in a pediatric case of chronic myeloid leukemia in B-cell lymphoid blast crisis. Leuk Res. 36:195–198. 2012. View Article : Google Scholar | |
Wu HK, Heng HH, Siderovski DP, et al: Identification of a human LIM-Hox gene, hLH-2, aberrantly expressed in chronic myelogenous leukaemia and located on 9q33–34.1. Oncogene. 12:1205–1212. 1996.PubMed/NCBI | |
Wu HK and Minden MD: Transcriptional activation of human LIM-HOX gene, hLH-2, in chronic myelogenous leukemia is due to a cis-acting effect of Bcr-Abl. Biochem Biophys Res Commun. 233:806–812. 1997.PubMed/NCBI | |
Gorantla B, Asuthkar S, Rao JS, Patel J and Gondi CS: Suppression of the uPAR-uPA system retards angiogenesis, invasion, and in vivo tumor development in pancreatic cancer cells. Mol Cancer Res. 9:377–389. 2011. View Article : Google Scholar : PubMed/NCBI | |
Tiede S and Paus R: Lhx2-decisive role in epithelial stem cell maintenance, or just the ‘tip of the iceberg’? Bioessays. 28:1157–1160. 2006.PubMed/NCBI | |
Abate-Shen C: Deregulated homeobox gene expression in cancer: cause or consequence? Nat Rev Cancer. 2:777–785. 2002. View Article : Google Scholar : PubMed/NCBI | |
Rahmatpanah FB, Carstens S, Guo J, et al: Differential DNA methylation patterns of small B-cell lymphoma subclasses with different clinical behavior. Leukemia. 20:1855–1862. 2006. View Article : Google Scholar : PubMed/NCBI | |
Kim MS, Lee J, Oh T, et al: Genome-wide identification of OTP gene as a novel methylation marker of breast cancer. Oncol Rep. 27:1681–1688. 2012.PubMed/NCBI | |
Kamalakaran S, Varadan V, Giercksky Russnes HE, et al: DNA methylation patterns in luminal breast cancers differ from non-luminal subtypes and can identify relapse risk independent of other clinical variables. Mol Oncol. 5:77–92. 2011. View Article : Google Scholar | |
Rauch T, Li H, Wu X and Pfeifer GP: MIRA-assisted microarray analysis, a new technology for the determination of DNA methylation patterns, identifies frequent methylation of homeodomain-containing genes in lung cancer cells. Cancer Res. 66:7939–7947. 2006. View Article : Google Scholar | |
Sharma K, Sheng HZ, Lettieri K, et al: LIM homeodomain factors Lhx3 and Lhx4 assign subtype identities for motor neurons. Cell. 95:817–828. 1998. View Article : Google Scholar : PubMed/NCBI | |
Sheng HZ, Zhadanov AB, Mosinger B Jr, et al: Specification of pituitary cell lineages by the LIM homeobox gene Lhx3. Science. 272:1004–1007. 1996. View Article : Google Scholar : PubMed/NCBI | |
Sheng HZ, Moriyama K, Yamashita T, et al: Multistep control of pituitary organogenesis. Science. 278:1809–1812. 1997. View Article : Google Scholar : PubMed/NCBI | |
Thaler JP, Lee SK, Jurata LW, Gill GN and Pfaff SL: LIM factor Lhx3 contributes to the specification of motor neuron and interneuron identity through cell-type-specific protein-protein interactions. Cell. 110:237–249. 2002. View Article : Google Scholar : PubMed/NCBI | |
Dietrich D, Lesche R, Tetzner R, et al: Analysis of DNA methylation of multiple genes in microdissected cells from formalin-fixed and paraffin-embedded tissues. J Histochem Cytochem. 57:477–489. 2009. View Article : Google Scholar : PubMed/NCBI | |
Li H, Witte DP, Branford WW, et al: Gsh-4 encodes a LIM-type homeodomain, is expressed in the developing central nervous system and is required for early postnatal survival. EMBO J. 13:2876–2885. 1994.PubMed/NCBI | |
Liu Y, Fan M, Yu S, et al: cDNA cloning, chromosomal localization and expression pattern analysis of human LIM-homeobox gene LHX4. Brain Res. 928:147–155. 2002. View Article : Google Scholar : PubMed/NCBI | |
Machinis K, Pantel J, Netchine I, et al: Syndromic short stature in patients with a germline mutation in the LIM homeobox LHX4. Am J Hum Genet. 69:961–968. 2001. View Article : Google Scholar : PubMed/NCBI | |
Raetzman LT, Ward R and Camper SA: Lhx4 and Prop1 are required for cell survival and expansion of the pituitary primordia. Development. 129:4229–4239. 2002.PubMed/NCBI | |
Kawamata N, Sakajiri S, Sugimoto KJ, Isobe Y, Kobayashi H and Oshimi K: A novel chromosomal translocation t(1;14)(q25;q32) in pre-B acute lymphoblastic leukemia involves the LIM homeo-domain protein gene, Lhx4. Oncogene. 21:4983–4991. 2002. View Article : Google Scholar : PubMed/NCBI | |
Yamaguchi M, Yamamoto K and Miura O: Aberrant expression of the LHX4 LIM homeobox gene caused by t(1;14)(q25;q32) in chronic myelogenous leukemia in biphenotypic blast crisis. Genes Chromosomes Cancer. 38:269–273. 2003. View Article : Google Scholar : PubMed/NCBI | |
de Bruijn DR, van Dijk AH, Willemse MP and van Kessel AG: The C terminus of the synovial sarcoma-associated SSX proteins interacts with the LIM homeobox protein LHX4. Oncogene. 27:653–662. 2008.PubMed/NCBI | |
Goc A, Kochuparambil ST, Al-Husein B, Al-Azayzih A, Mohammad S and Somanath PR: Simultaneous modulation of the intrinsic and extrinsic pathways by simvastatin in mediating prostate cancer cell apoptosis. BMC Cancer. 12:4092012. View Article : Google Scholar : PubMed/NCBI | |
Hung TM, Hu RH, Ho CM, et al: Downregulation of alpha-fetoprotein expression by LHX4: a critical role in hepatocarcinogenesis. Carcinogenesis. 32:1815–1823. 2011. View Article : Google Scholar : PubMed/NCBI | |
Zhao Y, Hermesz E, Yarolin MC and Westphal H: Genomic structure, chromosomal localization and expression of the human LIM-homeobox gene LHX5. Gene. 260:95–101. 2000. View Article : Google Scholar : PubMed/NCBI | |
Sheng HZ, Bertuzzi S, Chiang C, et al: Expression of murine Lhx5 suggests a role in specifying the forebrain. Dev Dyn. 208:266–277. 1997. View Article : Google Scholar : PubMed/NCBI | |
Zhao Y, Sheng HZ, Amini R, et al: Control of hippocampal morphogenesis and neuronal differentiation by the LIM homeobox gene Lhx5. Science. 284:1155–1158. 1999. View Article : Google Scholar : PubMed/NCBI | |
Grigoriou M, Tucker AS, Sharpe PT and Pachnis V: Expression and regulation of Lhx6 and Lhx7, a novel subfamily of LIM homeodomain encoding genes, suggests a role in mammalian head development. Development. 125:2063–2074. 1998. | |
Estécio MR, Youssef EM, Rahal P, et al: LHX6 is a sensitive methylation marker in head and neck carcinomas. Oncogene. 25:5018–5026. 2006.PubMed/NCBI | |
Jung S, Jeong D, Kim J, et al: Epigenetic regulation of the potential tumor suppressor gene, hLHX6.1, in human cervical cancer. Int J Oncol. 38:859–869. 2011.PubMed/NCBI | |
Jung S, Jeong D, Kim J, et al: The role of hLHX6-HMR as a methylation biomarker for early diagnosis of cervical cancer. Oncol Rep. 23:1675–1682. 2010. | |
Failli V, Rogard M, Mattei MG, Vernier P and Rétaux S: Lhx9 and Lhx9α LIM-homeodomain factors: genomic structure, expression patterns, chromosomal localization, and phylogenetic analysis. Genomics. 64:307–317. 2000. | |
Vladimirova V, Mikeska T, Waha A, et al: Aberrant methylation and reduced expression of LHX9 in malignant gliomas of childhood. Neoplasia. 11:700–711. 2009.PubMed/NCBI | |
Bennett LB, Schnabel JL, Kelchen JM, et al: DNA hypermethylation accompanied by transcriptional repression in follicular lymphoma. Genes Chromosomes Cancer. 48:828–841. 2009. View Article : Google Scholar : PubMed/NCBI | |
Karlsson O, Thor S, Norberg T, Ohlsson H and Edlund T: Insulin gene enhancer binding protein Isl-1 is a member of a novel class of proteins containing both a homeo-and a Cys His domain. Nature. 344:879–882. 1990. View Article : Google Scholar : PubMed/NCBI | |
Ahlgren U, Pfaff SL, Jessell TM, Edlund T and Edlund H: Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells. Nature. 385:257–260. 1997. View Article : Google Scholar : PubMed/NCBI | |
Yamada T, Pfaff SL, Edlund T and Jessell TM: Control of cell pattern in the neural tube: motor neuron induction by diffusible factors from notochord and floor plate. Cell. 73:673–686. 1993. View Article : Google Scholar : PubMed/NCBI | |
Jensen J: Gene regulatory factors in pancreatic development. Dev Dyn. 229:176–200. 2004. View Article : Google Scholar : PubMed/NCBI | |
Dong J, Asa SL and Drucker DJ: Islet cell and extrapancreatic expression of the LIM domain homeobox gene isl-1. Mol Endocrinol. 5:1633–1641. 1991. View Article : Google Scholar : PubMed/NCBI | |
Graham RP, Shrestha B, Caron BL, et al: Islet-1 is a sensitive but not entirely specific marker for pancreatic neuroendocrine neoplasms and their metastases. Am J Surg Pathol. 37:399–405. 2013. View Article : Google Scholar : PubMed/NCBI | |
Koo J, Mertens RB, Mirocha JM, Wang HL and Dhall D: Value of Islet 1 and PAX8 in identifying metastatic neuroendocrine neoplasms of pancreatic origin. Mod Pathol. 25:893–902. 2012. View Article : Google Scholar : PubMed/NCBI | |
Schmitt AM, Riniker F, Anlauf M, et al: Islet 1 (Isl1) expression is a reliable marker for pancreatic endocrine neoplasms and their metastases. Am J Surg Pathol. 32:420–425. 2008. View Article : Google Scholar : PubMed/NCBI | |
Hermann G, Konukiewitz B, Schmitt A, Perren A and Klöppel G: Hormonally defined pancreatic and duodenal neuroendocrine tumors differ in their transcription factor signatures: expression of ISL1, PDX1, NGN3, and CDX2. Virchows Arch. 459:147–154. 2011. View Article : Google Scholar | |
Cheung IY, Feng Y, Gerald W and Cheung NK: Exploiting gene expression profiling to identify novel minimal residual disease markers of neuroblastoma. Clin Cancer Res. 14:7020–7027. 2008. View Article : Google Scholar : PubMed/NCBI | |
Chizhikov VV, Lindgren AG, Mishima Y, et al: Lmx1a regulates fates and location of cells originating from the cerebellar rhombic lip and telencephalic cortical hem. Proc Natl Acad Sci USA. 107:10725–10730. 2010. View Article : Google Scholar : PubMed/NCBI | |
Cai J, Donaldson A, Yang M, German MS, Enikolopov G and Iacovitti L: The role of Lmx1a in the differentiation of human embryonic stem cells into midbrain dopamine neurons in culture and after transplantation into a Parkinson’s disease model. Stem Cell. 27:220–229. 2009.PubMed/NCBI | |
Lin CK, Chao TK, Lai HC and Lee HS: LMX1A as a prognostic marker in ovarian mucinous cystadenocarcinoma. Am J Clin Pathol. 137:971–977. 2012. View Article : Google Scholar : PubMed/NCBI | |
Tsai WC, Lee HS, Lin CK, Chen A, Nieh S and Ma HI: The association of osteopontin and LMX1A expression with World Health Organization grade in meningiomas and gliomas. Histopathology. 61:844–856. 2012. View Article : Google Scholar : PubMed/NCBI | |
Tsai WC, Lin CK, Yang YS, et al: The correlations of LMX1A and osteopontin expression to the clinicopathologic stages in pancreatic adenocarcinoma. Appl Immunohistochem Mol Morphol. 21:395–400. 2013. View Article : Google Scholar : PubMed/NCBI | |
Liu CY, Chao TK, Su PH, et al: Characterization of LMX-1A as a metastasis suppressor in cervical cancer. J Pathol. 219:222–231. 2009. View Article : Google Scholar : PubMed/NCBI | |
Lai HC, Lin YW, Huang TH, et al: Identification of novel DNA methylation markers in cervical cancer. Int J Cancer. 123:161–167. 2008. View Article : Google Scholar : PubMed/NCBI | |
Lai HC, Lin YW, Huang RL, et al: Quantitative DNA methylation analysis detects cervical intraepithelial neoplasms type 3 and worse. Cancer. 116:4266–4274. 2010. View Article : Google Scholar : PubMed/NCBI | |
Chao TK, Yo YT, Liao YP, et al: LIM-homeobox transcription factor 1, alpha (LMX1A) inhibits tumourigenesis, epithelial-mesenchymal transition and stem-like properties of epithelial ovarian cancer. Gynecol Oncol. 128:475–482. 2013. View Article : Google Scholar | |
Su HY, Lai HC, Lin YW, et al: An epigenetic marker panel for screening and prognostic prediction of ovarian cancer. Int J Cancer. 124:387–393. 2009. View Article : Google Scholar : PubMed/NCBI | |
Zhao Y, Guo S, Sun J, et al: Methylcap-seq reveals novel DNA methylation markers for the diagnosis and recurrence prediction of bladder cancer in a Chinese population. PLoS One. 7:e351752012. View Article : Google Scholar : PubMed/NCBI | |
Dong W, Feng L, Xie Y, Zhang H and Wu Y: Hypermethylation-mediated reduction of LMX1A expression in gastric cancer. Cancer Sci. 102:361–366. 2011. View Article : Google Scholar : PubMed/NCBI | |
Paz MF, Wei S, Cigudosa JC, et al: Genetic unmasking of epigenetically silenced tumor suppressor genes in colon cancer cells deficient in DNA methyltransferases. Hum Mol Genet. 12:2209–2219. 2003. View Article : Google Scholar : PubMed/NCBI | |
Chen H, Lun Y, Ovchinnikov D, et al: Limb and kidney defects in Lmx1b mutant mice suggest an involvement of LMX1B in human nail patella syndrome. Nat Genet. 19:51–55. 1998. | |
Riddle RD, Ensini M, Nelson C, Tsuchida T, Jessell TM and Tabin C: Induction of the LIM homeobox gene Lmx1 by WNT7a establishes dorsoventral pattern in the vertebrate limb. Cell. 83:631–640. 1995.PubMed/NCBI | |
Rieger ME, Sims AH, Coats ER, Clarke RB and Briegel KJ: The embryonic transcription cofactor LBH is a direct target of the Wnt signaling pathway in epithelial development and in aggressive basal subtype breast cancers. Mol Cell Biol. 30:4267–4279. 2010. View Article : Google Scholar | |
Kengaku M, Capdevila J, Rodriguez-Esteban C, et al: Distinct WNT pathways regulating AER formation and dorsoventral polarity in the chick limb bud. Science. 280:1274–1277. 1998. View Article : Google Scholar : PubMed/NCBI | |
Clevers H: Wnt/β-catenin signaling in development and disease. Cell. 127:469–480. 2006. | |
Millen KJ, Millonig JH and Hatten ME: Roof plate and dorsal spinal cord dl1 interneuron development in the dreher mutant mouse. Dev Biol. 270:382–392. 2004. View Article : Google Scholar : PubMed/NCBI | |
Chizhikov VV and Millen KJ: Control of roof plate formation by Lmx1a in the developing spinal cord. Development. 131:2693–2705. 2004. View Article : Google Scholar : PubMed/NCBI | |
Kishigami S and Mishina Y: BMP signaling and early embryonic patterning. Cytokine Growth Factor Rev. 16:265–278. 2005. View Article : Google Scholar : PubMed/NCBI | |
Dormoy V, Jacqmin D, Lang H and Massfelder T: From development to cancer: lessons from the kidney to uncover new therapeutic targets. Anticancer Res. 32:3609–3617. 2012.PubMed/NCBI | |
Sato A and Shibuya H: WNK signaling is involved in neural development via Lhx8/Awh expression. PLoS One. 8:e553012013. View Article : Google Scholar : PubMed/NCBI | |
Moriguchi T, Urushiyama S, Hisamoto N, et al: WNK1 regulates phosphorylation of cation-chloride-coupled cotransporters via the STE20-related kinases, SPAK and OSR1. J Biol Chem. 280:42685–42693. 2005. View Article : Google Scholar : PubMed/NCBI | |
Vitari AC, Deak M, Morrice NA and Alessi DR: The WNK1 and WNK4 protein kinases that are mutated in Gordon’s hypertension syndrome phosphorylate and activate SPAK and OSR1 protein kinases. Biochem J. 391:17–24. 2005.PubMed/NCBI | |
Moniz S and Jordan P: Emerging roles for WNK kinases in cancer. Cell Mol Life Sci. 67:1265–1276. 2010. View Article : Google Scholar : PubMed/NCBI | |
Veríssimo F and Jordan P: WNK kinases, a novel protein kinase subfamily in multi-cellular organisms. Oncogene. 20:5562–5569. 2001.PubMed/NCBI | |
Tu SW, Bugde A, Luby-Phelps K and Cobb MH: WNK1 is required for mitosis and abscission. Proc Natl Acad Sci USA. 108:1385–1390. 2011. View Article : Google Scholar : PubMed/NCBI | |
Sun X, Gao L, Yu RK and Zeng G: Down-regulation of WNK1 protein kinase in neural progenitor cells suppresses cell proliferation and migration. J Neurochem. 99:1114–1121. 2006. View Article : Google Scholar : PubMed/NCBI | |
Moniz S and Jordan P: Emerging roles for WNK kinases in cancer. Cell Mol Life Sci. 67:1265–1276. 2010. View Article : Google Scholar : PubMed/NCBI | |
Cohen ED, Wang Z, Lepore JJ, et al: Wnt/β-catenin signaling promotes expansion of Isl-1-positive cardiac progenitor cells through regulation of FGF signaling. J Clin Invest. 117:1794–1804. 2007. | |
Liem KF Jr, Jessell TM and Briscoe J: Regulation of the neural patterning activity of sonic hedgehog by secreted BMP inhibitors expressed by notochord and somites. Development. 127:4855–4866. 2000.PubMed/NCBI | |
Chizhikov VV and Millen KJ: Control of roof plate development and signaling by Lmx1b in the caudal vertebrate CNS. J Neurosci. 24:5694–5703. 2004. View Article : Google Scholar : PubMed/NCBI | |
Chizhikov VV and Millen KJ: Control of roof plate formation by Lmx1a in the developing spinal cord. Development. 131:2693–2705. 2004. View Article : Google Scholar : PubMed/NCBI | |
Alexandre P, Bachy I, Marcou M and Wassef M: Positive and negative regulations by FGF8 contribute to midbrain roof plate developmental plasticity. Development. 133:2905–2913. 2006. View Article : Google Scholar : PubMed/NCBI |