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

• Published in: Molecular cancer Vol. 9; no. 1; p. 62
• Main Authors: Spinola, Monica, Falvella, Felicia S, Colombo, Francesca, Sullivan, James P, Shames, David S, Girard, Luc, Spessotto, Paola, Minna, John D, Dragani, Tommaso A
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 17-03-2010; BioMed Central; BMC
• Subjects: Animals; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cell Adhesion - genetics; Cell cycle; Cell Cycle - genetics; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation; Colleges & universities; Down-Regulation - genetics; Extracellular Matrix - genetics; Extracellular Matrix - metabolism; Female; G1 Phase; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Generalized linear models; Genes, Tumor Suppressor; Genetic aspects; Humans; Immunohistochemistry; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; Mice; Mice, Nude; Ontology; Physiological aspects; Resting Phase, Cell Cycle; Risk factors; Rodents; Software; Statistical analysis; Tumor suppressor genes; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumors; United States; Italy; Dallas Texas
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/1476-4598-9-62

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