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The constitutive activation of the Src family kinases (SFKs) has been establishedas a poor prognostic factor in malignant mesothelioma (MM), however, the familymember(s) which contribute to the malignancy have not been defined. This studyaimed to identify the SFK member(s) contributing to cell growth using RNA interferencein various MM cell lines. Silencing of Yes but not of c-Src or Fyn in MM cellsleads to cell growth suppression. This suppressive effect caused by Yes silencingmainly depends on G1 cell cycle arrest and partly the induction of apoptosis.Also, the knockout of Yes induces the inactivation of β-catenin signaling andsubsequently decreases the levels of cyclin D necessary for G1-S transition inthe cell cycle. In addition, Yes knockout has less effect on cell growth suppressionin β-catenin-deficient H28 MM cells compared to other MM cells which express thecatenin. Overall, we conclude that Yes is a central mediator for MM cell growththat is not shared with other SFKs such as c-Src.

Yes is a central mediator of cell growth in malignant mesothelioma cells