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Differential Effects on Cell Motility, Embryonic Stem Cell Self-Renewal and Senescence by Diverse Src Kinase Family Inhibitors

Differential Effects on Cell Motility, Embryonic Stem Cell Self-Renewal and Senescence by Diverse Src Kinase Family Inhibitors

Christoffer Tamm, Sara Pijuan Galitó, Cecilia Annerén

Exp Cell Res. 2012 Feb 15;318(4):336-49.

PMID: 22197704

Abstract:

The Src family of non-receptor tyrosine kinases (SFKs) has been shown to play an intricate role in embryonic stem (ES) cell maintenance. In the present study we have focused on the underlying molecular mechanisms responsible for the vastly different effects induced by various commonly used SFK inhibitors. We show that several diverse cell types, including fibroblasts completely lacking SFKs, cannot undergo mitosis in response to SU6656 and that this is caused by an unselective inhibition of Aurora kinases. In contrast, PP2 and PD173952 block motility immediately upon exposure and forces cells to grow in dense colonies. The subsequent halt in proliferation of fibroblast and epithelial cells in the center of the colonies approximately 24 h post-treatment appears to be caused by cell-to-cell contact inhibition rather than a direct effect of SFK kinase inhibition. Interestingly, in addition to generating more homogenous and dense ES cell cultures, without any diverse effect on proliferation, PP2 and PD173652 also promote ES cell self-renewal by reducing the small amount of spontaneous differentiation typically observed under standard ES cell culture conditions. These effects could not be mirrored by the use of Gleevec, a potent inhibitor of c-Abl and PDGFR kinases that are also inhibited by PP2.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP305820751	PD173952		305820-75-1	Price

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