MFSD2A is a novel lung tumor suppressor gene modulating cell cycle and matrix attachment
1 Department of Predictive and for Prevention Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
2 Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, USA
3 Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
4 Divisione di Oncologia Sperimentale 2, Centro di Riferimento Oncologico di Aviano, Aviano, Italy
Molecular Cancer 2010, 9:62 doi:10.1186/1476-4598-9-62Published: 17 March 2010
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 (~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.