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Talin1 is an integrin regulatory protein that mediates integrin interactions with the extracellular matrix (ECM). This study investigated the significance of talin1 in prostate cancer progression to metastasis in vitro and in vivo. Talin1 overexpression enhanced prostate cancer cell adhesion, migration and invasion by activating survival signals and anoikis resistance. ShRNA-mediated talin1 loss led to a significant suppression of prostate cancer cell migration and transendothelial invasion in vitro and a significant inhibition of prostate cancer metastasis in vivo. Talin1 regulates cell survival signals via phosphorylation of focal adhesion kinase (FAK) and AKT. Targeting AKT activation led to a significant reduction of talin1-mediated prostate cancer cell invasion. Furthermore, talin1 expression was determined by immunostaining in prostate tissue from the TRAMP mouse model and in human prostate cancer specimens. Talin1 levels directly correlated with prostate tumor progression to metastasis in TRAMP mice. Talin1 profiling in human prostate specimens revealed a significantly higher expression of cytoplasmic talin1 in metastatic tissue compared to primary prostate tumors and benign prostate tissue (P<0.0001). This evidence suggests a potential value for talin1 as a marker of prostate cancer metastasis and implies that disrupting talin1 mediated signaling may have therapeutic significance in the treatment of metastatic disease.

Talin1 Promotes Prostate Cancer Invasion and Metastasis via AKT Signaling and Anoikis Resistance