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


CONCLUSIONS
Together these data suggest that MFSD2A is a novel lung cancer tumor suppressor gene that regulates cell cycle progression and matrix attachment.
Department of Predictive and for Prevention Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Monica
M
Spinola
Felicia S
FS
Falvella
Francesca
F
Colombo
James P
JP
Sullivan
David S
DS
Shames
Luc
L
Girard
Paola
P
Spessotto
John D
JD
Minna
Tommaso A
TA
Dragani
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D005260:Female; D016193:G1 Phase; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D016192:Resting Phase, Cell Cycle; D027981:Symporters; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
C549328:MFSD2A protein, human; D026901:Membrane Transport Proteins; D027981:Symporters; D025521:Tumor Suppressor Proteins