Talin2-mediated traction force drives matrix degradation and cell invasion.
Talin binds to β-integrin tails to activate integrins, regulating cell migration, invasion and metastasis. There are two talin genes, TLN1 and TLN2, encoding talin1 and talin2, respectively. Talin1 regulates focal adhesion dynamics, cell migration and invasion, whereas the biological function of talin2 is not clear and, indeed, talin2 has been presumed to function redundantly with talin1. Here, we show that talin2 has a much stronger binding to β-integrin tails than talin1. Replacement of talin2 Ser339 with Cys significantly decreased its binding to β1-integrin tails to a level comparable to that of talin1. Talin2 localizes at invadopodia and is indispensable for the generation of traction force and invadopodium-mediated matrix degradation. Ablation of talin2 suppressed traction force generation and invadopodia formation, which were restored by re-expressing talin2 but not talin1. Furthermore, re-expression of wild-type talin2 (but not talin2S339C) in talin2-depleted cells rescued development of traction force and invadopodia. These results suggest that a strong interaction of talin2 with integrins is required to generate traction, which in turn drives invadopodium-mediated matrix degradation, which is key to cancer cell invasion.
Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA Veterans Affairs Medical Center, Lexington, KY 40502, USA.
Lei
L
Qi
Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA Veterans Affairs Medical Center, Lexington, KY 40502, USA.
Naser
N
Jafari
Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA.
Xiang
X
Li
Department of Cell Biology & Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Zaozao
Z
Chen
Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA.
Liqing
L
Li
BioMediTech, University of Tampere, 33520 Tampere, Finland and Fimlab Laboratories, Tampere 33520, Finland.
Vesa P
VP
Hytönen
School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK.
Benjamin T
BT
Goult
Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, Lexington, KY 40506, USA.
Chang-Guo
CG
Zhan
Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA Veterans Affairs Medical Center, Lexington, KY 40502, USA Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40506, USA cai-huang@uky.edu.
Cai
0000-0003-4258-3841
C
Huang
D000818:Animals; D001696:Biomechanical Phenomena; D016466:CHO Cells; D002417:Cattle; D045744:Cell Line, Tumor; D002465:Cell Movement; D006224:Cricetinae; D003412:Cricetulus; D005109:Extracellular Matrix / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D000069261:Podosomes / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D016608:Talin / Q000378:metabolism*
D019012:Integrin beta1; D020033:Protein Isoforms; C518832:TLN1 protein, human; C436513:TLN2 protein, human; D016608:Talin
Cell invasion; Focal adhesions; Talin1; Talin2; Traction force
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