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 talin2WT in talin2-KO cells restored traction force generation and cell invasion, but that of talin2S339C, 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 talin2WT 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.

Document Type

Article

Publication Date

11-6-2017

Notes/Citation Information

Published in Oncotarget, v. 8, no. 63, p. 106876-106887.

Copyright: Li et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Digital Object Identifier (DOI)

https://doi.org/10.18632/oncotarget.22449

Funding Information

This work was supported by American Cancer Society Research Scholar Grant RSG-13-184-01CSM (to CH), and the National Institutes of Health Grants R01 GM122994 (to CH) and R01 CA195573 (to PR) as well as Shared Resource Facility of the University of Kentucky Markey Cancer Center (P30 CA177558).

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