PTP1B promotes cell proliferation and metastasis through activating src and ERK1/2 in non-small cell lung cancer

Cancer Lett. 2015 Apr 10;359(2):218-25. doi: 10.1016/j.canlet.2015.01.020. Epub 2015 Jan 21.

Abstract

Previous studies have demonstrated that protein tyrosine phosphatase 1B (PTP1B) can promote tumor progression in breast cancer, colon cancer and prostate cancer. Additionally, PTP1B acts as a tumor suppressor in other cancers, such as esophageal cancer and lymphoma. These findings suggest that PTP1B functions as a double-facet molecule in tumors, and the role of PTP1B in non-small cell lung cancer (NSCLC) is unknown. The present study demonstrates that the expression of PTP1B in NSCLC tissue is significantly higher than its expression in benign lung disease and is associated with the stage and overall survival (OS) of NSCLC patients. In vitro studies have demonstrated that PTP1B promotes the proliferation and metastasis of NSCLC cells by reducing the expression of p-src (Tyr527), which activates src and ERK1/2. This study provides the first exploration of the role of PTP1B in the proliferation and metastasis of NSCLC and subsequently elucidates the role of PTP1B in cancer. Our study uncovered that PTP1B can promote NSCLC proliferation and metastasis by activating src and subsequently ERK1/2 and provides a theoretical basis for future applications of PTP1B inhibitors in the treatment of NSCLC.

Keywords: Metastasis; Non-small cell lung cancer; Proliferation; Protein tyrosine phosphatase 1B; Src.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Animals
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / secondary
  • Cell Line, Tumor
  • Cell Proliferation*
  • Enzyme Activation
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lymphatic Metastasis
  • MAP Kinase Signaling System*
  • Male
  • Mice, SCID
  • Middle Aged
  • Neoplasm Transplantation
  • Proportional Hazards Models
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / physiology*
  • src-Family Kinases / metabolism*

Substances

  • src-Family Kinases
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1