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.
Highlights
Integrin-mediated mechanic signals regulate tumor cell migration, invasion, growth and metastasis [1,2,3,4,5,6]
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
We demonstrated that talin2 is localized at invadopodia and that a strong talin2-integrins interaction is required for traction force generation and invadopodium formation and cell invasion [25]
Summary
Integrin-mediated mechanic signals regulate tumor cell migration, invasion, growth and metastasis [1,2,3,4,5,6]. A large focal adhesion protein, binds to the β subunits, activating integrin and regulating a variety of physiological and pathological processes [8,9,10,11]. We have shown that talin phosphorylation by Cdk regulates FA dynamics, integrin activation, cell migration and invasion [13, 14]. It recruits the moesin-NHE1 complex to modulate pH at invadopodia, governing invadopodium stability and matrix degradation [19]. It was originally thought that talin functioned redundantly with talin
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