Over-expression of TM4SF1 improves cell metastasis and growth by activating ERK1/2 signaling pathway in human prostate cancer

J BUON. 2019 Nov-Dec;24(6):2531-2538.

Abstract

Purpose: To explore the effects of Transmembrane-4-L-six-family-1 (TM4SF1) in prostate cancer (PCa), and the related underlying mechanisms.

Methods: PCa tissues were obtained from 78 patients. PCa cell lines DU145 and RWPE-2 were purchased from American Type Culture Collection (ATCC). Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were conducted to analyze the expression of TM4SF1 in PCa tissues and DU145 cells. Plasmid containing over-expressed TM4SF1 was achieved by plasmid transfection. Transwell assay and wound-healing assay were designed to examine the invasion and migration of DU145 cells, whereas colony formation assay and 5-Ethynyl-2'- deoxyuridine (EdU) staining assay were performed to study the proliferation ability of DU145 cells.

Results: TM4SF1 was found over-expressed in PCa tissues and DU145 cells. Over-expression of TM4SF1 significantly activated the extracellular regulated protein kinases (ERK)1/2 signaling pathway, increased the epithelial-mesenchymal transition (EMT) expression, and enhanced the invasion, migration and proliferation of DU145 cells. Further studies revealed that suppression of ERK1/2 signaling pathway nearly resisted the positive effects on DU145 cells induced by TM4SF1 over-expression.

Conclusions: The present study demonstrated that TM4SF1 enhanced the invasion, migration and proliferation of DU145 cells by activating ERK1/2 signaling pathway.

MeSH terms

  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism*
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Movement
  • Cell Proliferation*
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Neoplasm Metastasis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Prognosis
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / secondary*
  • Tumor Cells, Cultured
  • Wound Healing

Substances

  • Antigens, Surface
  • Biomarkers, Tumor
  • Neoplasm Proteins
  • TM4SF1 protein, human
  • MAPK1 protein, human
  • MAPK3 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3