MFSD2A is a novel lung tumor suppressor gene modulating cell cycle and matrix attachment

Mol Cancer. 2010 Mar 17:9:62. doi: 10.1186/1476-4598-9-62.

Abstract

Background: MFSD2A (major facilitator superfamily domain containing 2) gene maps on chromosome 1p34 within a linkage disequilibrium block containing genetic elements associated with progression of lung cancer.

Results: Here we show that MFSD2A expression is strongly downregulated in non-small cell lung cancer cell lines of different histotypes and in primary lung adenocarcinomas. Experimental modulation of MFSD2A in lung cancer cells is associated with alteration of mRNA levels of genes involved in cell cycle control and interaction with the extracellular matrix. Exogenous expression of MFSD2A in lung cancer cells induced a G1 block, impaired adhesion and migration in vitro, and significantly reduced tumor colony number in vitro (4- to 27-fold, P < 0.0001) and tumor volume in vivo (approximately 3-fold, P < 0.0001). siRNA knockdown studies in normal human bronchial epithelial cells confirmed the role of MFSD2A in G1 regulation.

Conclusion: Together these data suggest that MFSD2A is a novel lung cancer tumor suppressor gene that regulates cell cycle progression and matrix attachment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Adhesion / genetics
  • Cell Cycle / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Down-Regulation / genetics
  • Extracellular Matrix / genetics
  • Extracellular Matrix / metabolism*
  • Female
  • G1 Phase
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor*
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Membrane Transport Proteins / genetics*
  • Membrane Transport Proteins / metabolism
  • Mice
  • Mice, Nude
  • Resting Phase, Cell Cycle
  • Symporters
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism

Substances

  • MFSD2A protein, human
  • Membrane Transport Proteins
  • Symporters
  • Tumor Suppressor Proteins