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. 2021 Feb 17;134(4):jcs254029. doi: 10.1242/jcs.254029

Fig. 3.

Fig. 3.

Roles of tensins in the regulation of cell migration, invasion and EMT. TNS1 promotes migration by interacting with DLC1, thereby suppressing the GTPase-activating protein (GAP) activity of DLC1 toward RhoA, and/or by linking pTyr-p130Cas to inwardly moving actin cytoskeleton. TNS1, TNS2 and TNS3 are critical for Rab25-dependent internalization of active integrins and this internalization is required for focal adhesion (FA) turnover and cell migration. EGF treatment activates a transcriptional switch that results in CTEN upregulation and TNS3 downregulation. Increased CTEN displaces TNS3 by binding to β1 integrin, but not actin filaments, leading to actin fiber reorganization that favors cell migration. Additionally, CTEN promotes cell migration, invasion and EMT by upregulating transforming growth factor β (TGF-β) and downstream effectors, including ILK, FAK, Src, Snail, Smad2 and α-smooth muscle actin (α-SMA). Moreover, TGF-β also induces CTEN expression, thus forming a positive-feedback loop.