Inactivation of Myocardin and p16 during Malignant Transformation Contributes to a Differentiation Defect

Michael Milyavsky, Igor Shats, Alina Cholostoy, Ran Brosh, Yosef Buganim, Lilach Weisz, Ira Kogan, Merav Cohen, Maria Shatz, Shalom Madar, Eyal Kalo, Naomi Goldfinger, Jun Yuan, Shulamit Ron, Karen MacKenzie, Amir Eden, Varda Rotter

Research output: Contribution to journalArticlepeer-review

Abstract

Myocardin is known as an important transcriptional regulator in smooth and cardiac muscle development. Here we found that myocardin is frequently repressed during human malignant transformation, contributing to a differentiation defect. We demonstrate that myocardin is a transcriptional target of TGFβ required for TGFβ-mediated differentiation of human fibroblasts. Serum deprivation, intact contact inhibition response, and the p16ink4a/Rb pathway contribute to myocardin induction and differentiation. Restoration of myocardin expression in sarcoma cells results in differentiation and inhibition of malignant growth, whereas inactivation of myocardin in normal fibroblasts increases their proliferative potential. Myocardin expression is reduced in multiple types of human tumors. Collectively, our results demonstrate that myocardin is an important suppressive modifier of the malignant transformation process.

Original languageEnglish
Pages (from-to)133-146
Number of pages14
JournalCancer Cell
Volume11
Issue number2
DOIs
StatePublished - 13 Feb 2007
Externally publishedYes

Keywords

  • CELLCYCLE

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