TY - JOUR
T1 - Talin2-mediated traction force drives matrix degradation and cell invasion
AU - Qi, Lei
AU - Jafari, Naser
AU - Li, Xiang
AU - Chen, Zaozao
AU - Li, Liqing
AU - Hytönen, Vesa P.
AU - Goult, Benjamin T.
AU - Zhan, Chang Guo
AU - Huang, Cai
N1 - Publisher Copyright:
© 2016. Published by The Company of Biologists Ltd.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Cell invasion
KW - Focal adhesions
KW - Talin1
KW - Talin2
KW - Traction force
UR - http://www.scopus.com/inward/record.url?scp=84995426960&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84995426960&partnerID=8YFLogxK
U2 - 10.1242/jcs.185959
DO - 10.1242/jcs.185959
M3 - Article
C2 - 27694340
AN - SCOPUS:84995426960
SN - 0021-9533
VL - 129
SP - 3661
EP - 3674
JO - Journal of Cell Science
JF - Journal of Cell Science
IS - 19
ER -