Molecular Oncology
Volume 1, Issue 1 , Pages 55-71 , June 2007

Functional role of Meox2 during the epithelial cytostatic response to TGF-β

  • Ulrich Valcourt

      Affiliations

    • Present address: Institut de Biologie et Chimie des Protéines (IBCP), UMR 5086 CNRS, Université Lyon 1, IFR 128 Biosciences Lyon-Gerland, 69367 Lyon Cedex 07, France.
    • These authors contributed equally to the work.
    • ,
  • Sylvie Thuault

      Affiliations

    • These authors contributed equally to the work.
    • ,
  • Katerina Pardali

      Affiliations

    • Present address: Molecular Medicine, Deptartment of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
    • These authors contributed equally to the work.
    • ,
  • Carl-Henrik Heldin
    • ,
  • Aristidis Moustakas

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +46 18 160414; Fax: +46 18 160420.

Received 6 December 2006 ,Revised 10 February 2007 ,Accepted 12 February 2007.

References 

  1. Andrés V, Fisher S, Wearsch P, Walsh K. Regulation of Gax homeobox gene transcription by a combination of positive factors including myocyte-specific enhancer factor 2. Mol. Cell. Biol. 1995;15:4272–4281
  2. Bachman KE, Blair BG, Brenner K, Bardelli A, Arena S, Zhou S, et al. p21WAF1/CIP1 mediates the growth response to TGF-β in human epithelial cells. Cancer Biol. Ther. 2004;3:221–225
  3. Candia AF, Hu J, Crosby J, Lalley PA, Noden D, Nadeau JH, et al. Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentially expressed during early mesodermal patterning in mouse embryos. Development. 1992;116:1123–1136
  4. Chen Y, Leal AD, Patel S, Gorski DH. The homeobox gene Gax activates p21WAF1/CIP1expression in vascular endothelial cells through direct interaction with upstream AT-rich sequences. J. Biol. Chem. 2007;282:507–517
  5. Cordenonsi M, Dupont S, Maretto S, Insinga A, Imbriano C, Piccolo S. Links between tumor suppressors: p53 is required for TGF-β gene responses by cooperating with Smads. Cell. 2003;113:301–314
  6. Datto MB, Li Y, Panus JF, Howe DJ, Xiong Y, Wang X-F. Transforming growth factor β induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism. Proc. Natl. Acad. Sci. USA. 1995;92:5545–5549
  7. Datto MB, Yu Y, Wang X-F. Functional analysis of the transforming growth factor beta responsive elements in the WAF1/Cip1/p21 promoter. J. Biol. Chem. 1995;270:28623–28628
  8. el-Deiry WS, Tokino T, Waldman T, Oliner JD, Velculescu VE, Burrell M, et al Topological control of p21WAF1/CIP1 expression in normal and neoplastic tissues. Cancer Res. 1995;55:2910–2919
  9. el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, et al. WAF1, a potential mediator of p53 tumor suppression. Cell. 1993;75:817–825
  10. Gorski DH, Leal AJ. Inhibition of endothelial cell activation by the homeobox gene Gax. J. Surg. Res. 2003;111:91–99
  11. Gorski DH, LePage DF, Patel CV, Copeland NG, Jenkins NA, Walsh K. Molecular cloning of a diverged homeobox gene that is rapidly down-regulated during the G0/G1 transition in vascular smooth muscle cells. Mol. Cell. Biol. 1993;13:3722–3733
  12. Huber MA, Kraut N, Beug H. Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr. Opin. Cell Biol. 2005;17:548–558
  13. Inman GJ, Nicolas FJ, Hill CS. Nucleocytoplasmic shuttling of Smads 2, 3, and 4 permits sensing of TGF- β receptor activity. Mol. Cell. 2002;10:283–294
  14. Jin JZ, Ding J. Analysis of Meox-2 mutant mice reveals a novel postfusion-based cleft palate. Dev Dyn. 2006;235:539–546
  15. Kowanetz M, Valcourt U, Bergström R, Heldin C-H, Moustakas A. Id2 and Id3 define the potency of cell proliferation and differentiation responses to tranforming growth factor β and bone morphogenetic protein. Mol. Cell. Biol. 2004;24:4241–4254
  16. Kurisaki K, Kurisaki A, Valcourt U, Terentiev AA, Pardali K, ten Dijke P, et al. Nuclear factor YY1 inhibits transforming growth factor β- and bone morphogenetic protein-induced cell differentiation. Mol. Cell. Biol. 2003;23:4494–4510
  17. Maillard L, Van Belle E, Smith RC, Le Roux A, Denéfle P, Steg G, et al. Percutaneous delivery of the gax gene inhibits vessel stenosis in a rabbit model of balloon angioplasty. Cardiovasc. Res. 1997;35:536–546
  18. Mankoo BS, Collins NS, Ashby P, Grigorieva E, Pevny LH, Candia A, et al. Mox2 is a component of the genetic hierarchy controlling limb muscle development. Nature. 1999;400:69–73
  19. Massagué J. How cells read TGF-β signals. Nat. Rev. Mol. Cell. Biol. 2000;1:169–178
  20. Massagué J. G1 cell-cycle control and cancer. Nature. 2004;432:298–306
  21. Morén A, Imamura T, Miyazono K, Heldin C-H, Moustakas A. Degradation of the tumor suppressor Smad4 by WW and HECT domain ubiquitin ligases. J. Biol. Chem. 2005;280:22115–22123
  22. Moustakas A, Kardassis D. Regulation of the human p21/WAF1/Cip1 promoter in hepatic cells by functional interactions between Sp1 and Smad family members. Proc. Natl. Acad. Sci. USA. 1998;95:6733–6738
  23. Moustakas A, Pardali K, Gaal A, Heldin C-H. Mechanisms of TGF-β signaling in regulation of cell growth and differentiation. Immunol. Lett. 2002;82:85–91
  24. Nicolas FJ, Hill CS. Attenuation of the TGF-β-Smad signaling pathway in pancreatic tumor cells confers resistance to TGF-β-induced growth arrest. Oncogene. 2003;22:3698–3711
  25. Pardali K, Kowanetz M, Heldin C-H, Moustakas A. Smad pathway-specific transcriptional regulation of the cell cycle inhibitor p21WAF1/Cip1. J. Cell. Physiol. 2005;204:260–272
  26. Pardali K, Kurisaki A, Morén A, ten Dijke P, Kardassis D, Moustakas A. Role of Smad proteins and transcription factor Sp1 in p21Waf1/Cip1 regulation by transforming growth factor-β. J. Biol. Chem. 2000;275:29244–29256
  27. Pardali K, Moustakas A. Actions of TGF-β as tumor suppressor and pro-metastatic factor in human cancer. Biochim. Biophys. Acta. 2007;1775:21–62
  28. Patel S, Leal AD, Gorski DH. The homeobox gene Gax inhibits angiogenesis through inhibition of nuclear factor-κB-dependent endothelial cell gene expression. Cancer Res. 2005;65:1414–1424
  29. Perlman H, Sata M, Le Roux A, Sedlak TW, Branellec D, Walsh K. Bax-mediated cell death by the Gax homeoprotein requires mitogen activation but is independent of cell cycle activity. EMBO J. 1998;17:3576–3586
  30. Quinn LM, Latham SE, Kalionis B. The homeobox genes MSX2 and MOX2 are candidates for regulating epithelial–mesenchymal cell interactions in the human placenta. Placenta. 2000;21(Suppl. A):S50–S54
  31. Rodrigo I, Bovolenta P, Mankoo BS, Imai K. Meox homeodomain proteins are required for Bapx1 expression in the sclerotome and activate its transcription by direct binding to its promoter. Mol. Cell. Biol. 2004;24:2757–2766
  32. Schonherr E, Levkau B, Schaefer L, Kresse H, Walsh K. Decorin-mediated signal transduction in endothelial cells. Involvement of Akt/protein kinase B in up-regulation of p21WAF1/CIP1 but not p27KIP1. J. Biol. Chem. 2001;276:40687–40692
  33. Seoane J, Le HV, Shen L, Anderson SA, Massagué J. Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell. 2004;117:211–223
  34. Shi Y, Massagué J. Mechanisms of TGF-β signaling from cell membrane to the nucleus. Cell. 2003;113:685–700
  35. Siegel PM, Massagué J. Cytostatic and apoptotic actions of TGF-β in homeostasis and cancer. Nat. Rev. Cancer. 2003;3:807–820
  36. Skopicki HA, Lyons GE, Schatteman G, Smith RC, Andrés V, Schirm S, et al. Embryonic expression of the Gax homeodomain protein in cardiac, smooth, and skeletal muscle. Circ. Res. 1997;80:452–462
  37. Smith RC, Branellec D, Gorski DH, Guo K, Perlman H, Dedieu JF, et al. p21CIP1-mediated inhibition of cell proliferation by overexpression of the gax homeodomain gene. Genes Dev. 1997;11:1674–1689
  38. ten Dijke P, Goumans M-J, Itoh F, Itoh S. Regulation of cell proliferation by Smad proteins. J. Cell. Physiol. 2002;191:1–16
  39. ten Dijke P, Hill CS. New insights into TGF-β-Smad signalling. Trends Biochem. Sci. 2004;29:265–273
  40. Thuault S, Valcourt U, Petersen M, Manfioletti G, Heldin C-H, Moustakas A. Transforming growth factor-β employs HMGA2 to elicit epithelial–mesenchymal transition. J. Cell Biol. 2006;174:175–183
  41. Valcourt U, Gouttenoire J, Moustakas A, Herbage D, Mallein-Gerin F. Functions of transforming growth factor-β family type I receptors and Smad proteins in the hypertrophic maturation and osteoblastic differentiation of chondrocytes. J. Biol. Chem. 2002;277:33545–33558
  42. Valcourt U, Kowanetz M, Niimi H, Heldin C-H, Moustakas A. TGF-β and the Smad signaling pathway support transcriptomic reprogramming during epithelial–mesenchymal cell transition. Mol. Biol. Cell. 2005;16:1987–2002
  43. Witzenbichler B, Kureishi Y, Luo Z, Le Roux A, Branellec D, Walsh K. Regulation of smooth muscle cell migration and integrin expression by the Gax transcription factor. J. Clin. Invest. 1999;104:1469–1480
  44. Wu Z, Guo H, Chow N, Sallstrom J, Bell RD, Deane R, et al Role of the MEOX2 homeobox gene in neurovascular dysfunction in Alzheimer disease. Nat. Med. 2005;11:959–965

PII: S1574-7891(07)00005-1

doi: 10.1016/j.molonc.2007.02.002

Molecular Oncology
Volume 1, Issue 1 , Pages 55-71 , June 2007

Article Tools

* Image Usage & Resolution