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Phosphorylation and interaction of myopodin by integrin-link kinase lead to suppression of cell growth and motility in prostate cancer cells

Oncogene volume 30, pages 4855–4863 (2011)Cite this article

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Abstract

Myopodin is a tumor-suppressor gene that suppresses growth of prostate and urothelial carcinomas. However, the mechanism of myopodin tumor-suppressor activity or signaling that leads to activation of myopodin remains unclear. In this report, we showed that the N-terminus of myopodin binds integrin-linked kinase (ILK) both in vivo and in vitro. An ILK interaction motif of 78 amino acids (amino acids 82–157) was identified in the N-terminus region of myopodin. Induction of ILK-dependent kinase activity by integrin α7 led to phosphorylation of myopodin both in vivo and in vitro. Knocking down ILK dramatically reduced the inhibition of cell growth and motility mediated by myopodin. A mutant of myopodin lacking the ILK interaction motif is inactive in suppressing the growth and motility of PC3 cells. As a result, this study showed a novel and critical signaling pathway that leads to activation of myopodin.

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References

  • Acconcia F, Barnes CJ, Singh RR, Talukder AH, Kumar R . (2007). Phosphorylation-dependent regulation of nuclear localization and functions of integrin-linked kinase. Proc Natl Acad Sci USA 104: 6782–6787.

    Article  CAS  Google Scholar 

  • Apte U, Gkretsi V, Bowen WC, Mars WM, Luo JH, Donthamsetty S et al. (2009). Enhanced liver regeneration following changes induced by hepatocyte-specific genetic ablation of integrin-linked kinase. Hepatology 50: 844–851.

    Article  CAS  Google Scholar 

  • Cebrian V, Alvarez M, Aleman A, Palou J, Bellmunt J, Gonzalez-Peramato P et al. (2008). Discovery of myopodin methylation in bladder cancer. J Pathol 216: 111–119.

    Article  CAS  Google Scholar 

  • Deng JT, Van Lierop JE, Sutherland C, Walsh MP . (2001). Ca2+-independent smooth muscle contraction. A novel function for integrin-linked kinase. J Biol Chem 276: 16365–16373.

    Article  CAS  Google Scholar 

  • Donthamsetty S, Bowen W, Mars W, Bhave V, Luo JH, Wu C et al. (2010). Liver specific ablation of integrin linked kinase (ILK) in mice results in enhanced and prolonged cell proliferation and hepatomegaly after phenobarbital administration. Toxicol Sci 113: 358–366.

    Article  CAS  Google Scholar 

  • Gkretsi V, Apte U, Mars WM, Bowen WC, Luo JH, Yang Y et al. (2008). Liver-specific ablation of integrin-linked kinase in mice results in abnormal histology, enhanced cell proliferation, and hepatomegaly. Hepatology 48: 1932–1941.

    Article  Google Scholar 

  • Han YC, Yu YP, Nelson J, Wu C, Wang H, Michalopoulos GK et al. (2010). Interaction of integrin-linked kinase and miniature chromosome maintenance 7-mediating integrin {alpha}7 induced cell growth suppres. Cancer Res 70: 4375–4384.

    Article  CAS  Google Scholar 

  • Hannigan GE, Leung-Hagesteijn C, Fitz-Gibbon L, Coppolino MG, Radeva G, Filmus J et al. (1996). Regulation of cell adhesion and anchorage-dependent growth by a new beta 1-integrin-linked protein kinase. Nature 379: 91–96.

    Article  CAS  Google Scholar 

  • Jing L, Liu L, Yu YP, Dhir R, Acquafondada M, Landsittel D et al. (2004). Expression of myopodin induces suppression of tumor growth and metastasis. Am J Pathol 164: 1799–1806.

    Article  CAS  Google Scholar 

  • Legate KR, Montanez E, Kudlacek O, Fassler R . (2006). ILK, PINCH and parvin: the tIPP of integrin signalling. Nat Rev Mol Cell Biol 7: 20–31.

    Article  CAS  Google Scholar 

  • Lin F, Yu YP, Woods J, Cieply K, Gooding B, Finkelstein P et al. (2001). Myopodin, a synaptopodin homologue, is frequently deleted in invasive prostate cancers. Am J Pathol 159: 1603–1612.

    Article  CAS  Google Scholar 

  • Persad S, Attwell S, Gray V, Mawji N, Deng JT, Leung D et al. (2001). Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and amino acids arginine 211 and serine 343. J Biol Chem 276: 27462–27469.

    Article  CAS  Google Scholar 

  • Ren B, Yu YP, Tseng GC, Wu C, Chen K, Rao UN et al. (2007). Analysis of integrin alpha7 mutations in prostate cancer, liver cancer, glioblastoma multiforme, and leiomyosarcoma. J Natl Cancer Inst 99: 868–880.

    Article  CAS  Google Scholar 

  • Sakai T, Li S, Docheva D, Grashoff C, Sakai K, Kostka G et al. (2003). Integrin-linked kinase (ILK) is required for polarizing the epiblast, cell adhesion, and controlling actin accumulation. Genes Dev 17: 926–940.

    Article  CAS  Google Scholar 

  • Sanchez-Carbayo M, Schwarz K, Charytonowicz E, Cordon-Cardo C, Mundel P . (2003). Tumor suppressor role for myopodin in bladder cancer: loss of nuclear expression of myopodin is cell-cycle dependent and predicts clinical outcome. Oncogene 22: 5298–5305.

    Article  CAS  Google Scholar 

  • Wu C . (2004). The PINCH-ILK-parvin complexes: assembly, functions and regulation. Biochim Biophys Acta 1692: 55–62.

    Article  CAS  Google Scholar 

  • Yamaji S, Suzuki A, Sugiyama Y, Koide Y, Yoshida M, Kanamori H et al. (2001). A novel integrin-linked kinase-binding protein, affixin, is involved in the early stage of cell-substrate interaction. J Cell Biol 153: 1251–1264.

    Article  CAS  Google Scholar 

  • Yu YP, Luo JH . (2006). Myopodin-mediated suppression of prostate cancer cell migration involves interaction with zyxin. Cancer Res 66: 7414–7419.

    Article  CAS  Google Scholar 

  • Yu YP, Tseng GC, Luo JH . (2006). Inactivation of myopodin expression associated with prostate cancer relapse. Urology 68: 578–582.

    Article  Google Scholar 

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Acknowledgements

This work was supported by grants from National Cancer Institute (R56 CA098249 and RO1 CA098249 to JHL) and American Cancer Society (RSG-08-137-01-CNE to YPY).

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  1. Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Y-P Yu & J-H Luo

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  1. Y-P Yu
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Correspondence to Y-P Yu.

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Yu, YP., Luo, JH. Phosphorylation and interaction of myopodin by integrin-link kinase lead to suppression of cell growth and motility in prostate cancer cells. Oncogene 30, 4855–4863 (2011). https://doi.org/10.1038/onc.2011.200

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