The role of talin2 in breast cancer tumorigenesis and metastasis

// Liqing Li 1, * , Xiang Li 1, * , Lei Qi 1 , Piotr Rychahou 1 , Naser Jafari 1 and Cai Huang 1, 2 1 Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA 2 Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40506, USA * These authors contributed equally to this work Correspondence to: Cai Huang, email: cai-huang@uky.edu Keywords: talin2; cell migration; invasion; tumor growth; metastasis Received: August 06, 2017 Accepted: October 25, 2017 Published: November 06, 2017 ABSTRACT Recent studies show that talin2 has a higher affinity to β-integrin tails and is indispensable for traction force generation and cell invasion. However, its roles in cell migration, cancer cell metastasis and tumorigenesis remain to be determined. Here, we used MDA-MB-231 human breast cancer cells as a model to define the roles of talin2 in cell migration, invasion, metastasis and tumorigenesis. We show here that talin2 knockdown (KD) inhibited cell migration and focal adhesion dynamics, a key step in cell migration, and that talin2 knockout (KO) inhibited cell invasion and traction force generation, the latter is crucial for cell invasion. Re-expression of talin2 WT in talin2-KO cells restored traction force generation and cell invasion, but that of talin2 S339C , a β-integrin-binding deficient mutant, did not. Moreover, talin2 KO (or KD) suppressed tumorigenesis and metastasis in mouse xenograft models. However, surprisingly, re-expression of talin2 WT in talin2-KO cells did not rescue tumorigenesis. Thus, talin2 is required for breast cancer cell migration, invasion, metastasis and tumorigenesis, although exogenous expression of high levels of talin2 could inhibit tumorigenesis.