TMEM176A acts as a tumor suppressor gene in pancreatic cancer by inhibiting ERK signaling

Discov Med. 2020 Nov-Dec;30(161):145-153.

Abstract

Background: Pancreatic cancer is the 7th leading cause of cancer-related death worldwide. Aberrant expressions of transmembrane 176A (TMEM176A) were found in multiple cancer types. However, the expression and function of TMEM176A remain unclear in pancreatic cancer.

Materials and methods: Immunohistochemistry, flow cytometry, western blot, and transwell were applied on investigating samples from pancreatic cancer patients and pancreatic cancer cell lines.

Results: Analysis based on the TCGA database showed that a high level of TMEM176A was associated with a better relapse-free survival rate (P = 0.012). Further, the results of tissue microarray showed patients with a high level of TMEM176A were associated with lymph node metastasis (P = 0.045) and a better overall survival rate (P = 0.032). Overexpression of TMEM176A in Capan-1 and PANC-1 cells suppressed cell proliferation, cell invasion, and migration, and induced apoptosis in pancreatic cancer cells. TMEM176A suppressed ERK signaling in pancreatic cancer.

Conclusion: TMEM176A suppresses the growth and migration of pancreatic cancer cells by inhibiting ERK signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Datasets as Topic
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor*
  • Humans
  • MAP Kinase Signaling System / genetics
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Pancreas / pathology
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • Tissue Array Analysis

Substances

  • Membrane Proteins
  • TMEM176A protein, human