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.

New Frontiers for the Cytoskeletal Protein LASP1

“…A similar problem occurred in the recent paper by Zhang et al when studying the effect of LASP2 on non-small cell lung cancer (NSCLC) and phosphorylation of focal adhesion kinase (FAK) ( 85 ). The used antibody, claimed to be specific for LASP2 was actually generated against nebulette (NEBL).…”

Knockdown of LASP2 inhibits the proliferation, migration, and invasion of cervical cancer cells

“…Further investigations prove that LASP2 promotes migration/invasion of NSCLC cells. 6 These findings imply that LASP2 acts as either oncogene or tumor suppressor in cancers. Our data showed LASP2 was highly expressed in cervical cancer.…”

“…These different roles of LASP2 in CRC could attribute to different race and sample sizes. Further investigations prove that LASP2 promotes migration/invasion of NSCLC cells . These findings imply that LASP2 acts as either oncogene or tumor suppressor in cancers.…”

Nebulette Expression Is Associated with Lymph Node Metastasis in Patients with Colorectal Cancer

“…Also expression of the gene is significantly correlated with histological type, TNM staging, lymph node metastasis, and predicted poor survival of patients with NSCLC. 9 NEBL is involved in mixed lineage leukemia (MLL) rearrangements and has an oncogenic role in leukemia. 20 …”

“…Although NEBL is down-regulated in CRC and suppresses CRC cell growth and migration, 8 it is over-expressed in the NSCLC (Non-Small Cell Lung Cancer) cells and enhances NSCLC invasion and cell migration. 9 …”