Upregulation of LASP2 inhibits pancreatic cancer cell migration and invasion through suppressing TGF-β-induced EMT

J Cell Biochem. 2019 Aug;120(8):13651-13657. doi: 10.1002/jcb.28638. Epub 2019 Apr 4.

Abstract

LASP2 (LIM and SH3 protein 2), a member of the LIM-protein subfamily of the nebulin group, was first identified as a splice variant of the nebulin gene. In the past, investigators mainly focused on the impact of LASP2 on cardiac diseases because of its identification in the myocardium. Recently, several studies have reported that LASP2 is associated with the progression of various cancers. However, there have been no investigations on the expression and function of LASP2 in pancreatic cancer (PC). In this study, we performed the quantitative real-time polymerase chain reaction and Western blot analysis to detect the expression of LASP2 in PC tissues and cell lines. PC cells were transfected with LASP2 overexpression plasmid or the negative control in the presence or absence of tumor growth factor-β (TGF-β). The transwell assays were used to measure the effects of LASP2 on PC cell migration and invasion. The protein expression of epithelial-mesenchymal transition (EMT) markers was detected using Western blot assay. Our results demonstrated that LASP2 was downregulated in PC tissues and cell lines. In addition, upregulation of LASP2 inhibited the PC cell migration and invasion. We also found that LASP2 upregulation reversed TGF-β-induced EMT in PC cells. Taken together, we provided novel evidence supporting the tumor-suppressor role of LASP2 in PC and suggested it as a potential therapeutic target in PC treatment.

Keywords: LASP2; epithelial-mesenchymal transition; invasion; migration; pancreatic cancer.

MeSH terms

  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / genetics
  • Cell Line, Tumor
  • Cell Movement*
  • Cytoskeletal Proteins / biosynthesis*
  • Cytoskeletal Proteins / genetics
  • Epithelial-Mesenchymal Transition*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • LIM Domain Proteins / biosynthesis*
  • LIM Domain Proteins / genetics
  • Neoplasm Invasiveness
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Up-Regulation*

Substances

  • Carrier Proteins
  • Cytoskeletal Proteins
  • LIM Domain Proteins
  • NEBL protein, human
  • Neoplasm Proteins
  • Transforming Growth Factor beta