Enhancement of in vitro cell motility and invasiveness of human malignant pleural mesothelioma cells through the HIF-1α-MUC1 pathway

Cancer Lett. 2013 Oct 1;339(1):82-92. doi: 10.1016/j.canlet.2013.07.020. Epub 2013 Jul 20.

Abstract

In this study, we examined the effects of hypoxia on the malignancy of human malignant pleural mesothelioma (MPM) cell lines, and found (1) hypoxia enhanced motility and invasiveness of human malignant pleural mesothelioma (MPM) cells; (2) this phenomenon resulted from increased expression of sialylated MUC1 through the activation of HIF-1 pathway; (3) two HIF-binding sites located in the promoter region of MUC1 were important for MUC1 transactivation under hypoxia. These findings are useful for better understanding molecular mechanisms of aggressive behavior of MPM cells and for targeting them in the clinical therapies for MPM patients.

Keywords: HIF; Hypoxia; Invasiveness; MUC1; Mesothelioma; Motility.

MeSH terms

  • Cell Hypoxia
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Mesothelioma / genetics
  • Mesothelioma / metabolism*
  • Mesothelioma / pathology
  • Mucin-1 / genetics
  • Mucin-1 / metabolism*
  • Neoplasm Invasiveness
  • Pleural Neoplasms / genetics
  • Pleural Neoplasms / metabolism*
  • Pleural Neoplasms / pathology
  • Signal Transduction*

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Mucin-1