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.
|Number of pages||14|
|Journal||Journal of Cell Science|
|State||Published - 2016|
Bibliographical noteFunding Information:
We thank Dr BerniWehrle-Haller for his participation in the project discussion; Dr Ken Jacobson (UNC-Chapel Hill) for the technique of traction force assays; Latifeh Azizi (University of Tampere) for her support in affinity assays; Drs Berni Wehrle-Haller, Ken Jacobson and Andrew Morris for critical reading of this manuscript. This work was supported by a start-up fund from Markey Cancer Center; University of Kentucky; and the American Cancer Society Institutional Research Grant [grant number 85-001-22] and Research Scholar Grant [grant number RSG-13-184-01CSM] (to C.H.); and a Biotechnology and Biological Sciences Research Council project grant [grant number BB/N007336/1] (to B.T.G.).
© 2016. Published by The Company of Biologists Ltd.
- Cell invasion
- Focal adhesions
- Traction force
ASJC Scopus subject areas
- Cell Biology