Mesothelioma cells breaking bad: loss of integrin α7 promotes cell motility and poor clinical outcomes in patients

J Pathol. 2015 Nov;237(3):282-4. doi: 10.1002/path.4587. Epub 2015 Aug 26.

Abstract

Mesothelioma is a disease of pleural cells lining the lungs which is often caused by exposure to asbestos. The molecular mechanism(s) that regulate the transformation of pleural mesothelioma cells to a migratory and malignant phenotype are unclear. In recent work published in this journal, Laszlo et al performed a set of elegant experiments to identify a key molecular mechanism that may explain the aggressive nature of this disease. Using patient-derived mesothelioma cells with high versus low migratory activity, the authors conducted a genome-wide expression analysis. They identified a significant reduction in ITGA7 expression only in highly migratory malignant pleural mesothelioma cells and showed that loss of ITGA7 expression was associated with methylation of the promoter. Forced expression of integrin α7 reversed the migratory phenotype of these cells. Finally, the authors identified a strong correlation between ITGA7 expression and patient survival. Together, these results identify expression of integrin α7 as a molecular mechanism for the aggressive migratory transformation of mesothelioma and identify a potentially novel diagnostic and therapeutic target.

Keywords: epigenetics; integrin α7; malignancy; mesothelioma.

Publication types

  • Comment

MeSH terms

  • Antigens, CD / metabolism*
  • Cell Movement*
  • Epigenesis, Genetic*
  • Humans
  • Integrin alpha Chains / metabolism*
  • Lung Neoplasms / metabolism*
  • Mesothelioma / metabolism*
  • Pleural Neoplasms / metabolism*
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Antigens, CD
  • Integrin alpha Chains
  • Tumor Suppressor Proteins