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

Mol Carcinog. 2017 Dec;56(12):2558-2565. doi: 10.1002/mc.22700. Epub 2017 Aug 3.

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.

Keywords: FAK; Lasp2; NSCLC; invasion and metastasis; prognosis.

MeSH terms

  • A549 Cells
  • Adult
  • Aged
  • Animals
  • Blotting, Western
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Female
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • Humans
  • Immunohistochemistry
  • LIM Domain Proteins / genetics
  • LIM Domain Proteins / metabolism*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness
  • Phosphorylation
  • Prognosis
  • RNA Interference
  • Survival Analysis
  • Transplantation, Heterologous

Substances

  • Carrier Proteins
  • Cytoskeletal Proteins
  • LIM Domain Proteins
  • NEBL protein, human
  • Focal Adhesion Protein-Tyrosine Kinases