Fhit regulates invasion of lung tumor cells.
In many types of cancers, the fragile histidine triad (Fhit) gene is frequently targeted by genomic alterations leading to a decrease or loss of gene and protein expression. Fhit has been described as a tumor suppressor gene because of its ability to induce apoptosis and to inhibit proliferation of tumor cells. Moreover, several studies have shown a correlation between the lack of Fhit expression and tumor aggressiveness, thus suggesting that Fhit could be involved in tumor progression. In this study, we explored the potential role of Fhit during tumor cell invasion. We first showed that a low Fhit expression is associated with in vivo and in vitro invasiveness of tumor cells. Then, we showed that Fhit overexpression in Fhit-negative highly invasive NCI-H1299 cells by transfection of Fhit cDNA and Fhit inhibition in Fhit-positive poorly invasive HBE4-E6/E7 cells by transfection of Fhit small interfering RNA induce, respectively, a decrease and an increase in migratory/invasive capacities. These changes in cell behavior were associated with a reorganization of tight and adherens junction molecules and a regulation of matrix metalloproteinase and vimentin expression. These results show that Fhit controls the invasive phenotype of lung tumor cells by regulating the expression of genes associated with epithelial-mesenchymal transition.
Joannes
A
A
INSERM, U903, Reims, France.
Bonnomet
A
A
Bindels
S
S
Polette
M
M
Gilles
C
C
Burlet
H
H
Cutrona
J
J
Zahm
J-M
JM
Birembaut
P
P
Nawrocki-Raby
B
B
D017766:Acid Anhydride Hydrolases / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D014408:Biomarkers, Tumor / Q000032:analysis; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000037:antagonists & inhibitors; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015316:Genetic Therapy; D005822:Genetic Vectors; D006639:Histidine / Q000378:metabolism; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000503:physiopathology / Q000517:prevention & control*; D009363:Neoplasm Proteins / Q000032:analysis / Q000494:pharmacology* / Q000502:physiology; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000473:pathology; D034741:RNA, Small Interfering / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D014408:Biomarkers, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006639:Histidine; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D053221:TNF-Related Apoptosis-Inducing Ligand; D025521:Tumor Suppressor Proteins; D000099170:Bis(5'-adenosyl)triphosphatase