Lasp2 enhances tumor invasion via facilitating phosphorylation of FAK and predicts poor overall survival of non-small cell lung cancer patients.

Abstract:

:Lasp2, as well as Lasp1, is a member of the LIM-protein subfamily of the nebulin group characterized by the combined presence of LIM and SH3 domains. Lasp1 and Lasp2 are highly conserved in their LIM, nebulin-like, and SH3 domains but differ significantly at their linker regions. Lasp1 had been described as an oncogenic protein that was highly expressed in diverse cancer types and facilitated tumor proliferation, invasion, and metastasis process. However, unlike Lasp1, little is known about the functions of Lasp2. In the present study, using immunohistochemistry, we found that Lasp2 expression was significantly correlated with histological type (P = 0.012), advanced TNM stage (P = 0.024), positive regional lymph node metastasis (P = 0.035), and poor overall survival (P = 0.001). Would healing assay and transwell assay results indicated that Lasp2 promoted tumor migration and invasion in NSCLC cells. Furthermore, Lasp2 facilitated Snail expression and inhibited Zo-1. The levels of phosphorylated FAK (Tyr397 and Tyr925) were obviously increased after overexpressing Lasp2 and were downregulated by transfecting Lasp2-siRNA. FAK inhibitor counteracted upregulating Snail expression and downregulating of Zo-1 expression induced by Lasp2 overexpression. Taken together, Lasp2 may facilitate tumor migration and invasion of NSCLCs through FAK-Snail/Zo-1 signaling pathway. Lasp2 may be a potential prognostic predictor of NSCLC patients.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

Zhang X,Cai L,Zhou H,Liu Y,Fan C,Wang L,Li A,Miao Y,Li Q,Qiu X,Wang E

doi

10.1002/mc.22700

subject

Has Abstract

pub_date

2017-12-01 00:00:00

pages

2558-2565

issue

12

eissn

0899-1987

issn

1098-2744

journal_volume

56

pub_type

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