LASP-1 induces proliferation, metastasis and cell cycle arrest at the G2/M phase in gallbladder cancer by down-regulating S100P via the PI3K/AKT pathway

Cancer Lett. 2016 Mar 28;372(2):239-50. doi: 10.1016/j.canlet.2016.01.008. Epub 2016 Jan 18.

Abstract

LASP-1 is an actin-binding protein that regulates cytoskeletal dynamics and cell migration. LASP-1 was previously identified in a cDNA library from metastatic breast cancer samples. This protein has since been detected in multiple human cancers, including liver cancer, gastric cancer and pancreatic cancer. S100P is a small calcium-binding protein in the S100 protein family that regulates cellular, physiological and pathological processes in various cancers. However, the clinical significance of LASP-1 and S100P expression in gallbladder cancer (GBC) is not yet clear. In our study, we focused on the clinical significance, biological function and mechanism of LASP-1 in gallbladder cancer and detected LASP-1 and S100P overexpression in GBC tissues. The expression of LASP-1 was significantly correlated with poor prognosis in GBC patients (P < 0.05). Furthermore, down-regulation of LASP-1 expression resulted in the obvious inhibition of proliferation and migration and caused cell cycle arrest by down-regulating S100P via the PI3K/AKT pathway; in mice, tumor volume was significantly decreased. In conclusion, LASP-1 may act as an oncogene to regulate the expression of S100P to influence cellular functions in GBC. LASP-1 could serve as a genetic treatment target in GBC patients.

Keywords: Cell cycle; Gallbladder cancer; LASP-1; Metastasis; Proliferation; S100P.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Aged
  • Animals
  • Calcium-Binding Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Down-Regulation
  • Female
  • G2 Phase Cell Cycle Checkpoints*
  • Gallbladder Neoplasms / enzymology*
  • Gallbladder Neoplasms / genetics
  • Gallbladder Neoplasms / pathology
  • Gallbladder Neoplasms / therapy
  • Gene Expression Regulation, Neoplastic
  • Humans
  • LIM Domain Proteins / genetics
  • LIM Domain Proteins / metabolism*
  • Male
  • Mice, Nude
  • Neoplasm Metastasis
  • Neoplasm Proteins / metabolism*
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA Interference
  • RNAi Therapeutics
  • Signal Transduction
  • Time Factors
  • Transfection
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • Adaptor Proteins, Signal Transducing
  • Calcium-Binding Proteins
  • Cytoskeletal Proteins
  • LASP1 protein, human
  • LIM Domain Proteins
  • Neoplasm Proteins
  • S100P protein, human
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt