Fhit regulates invasion of lung tumor cells

[en] 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.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Joannes, A.

Bonnomet, A.

Bindels, S.

Polette, M.

Gilles, Christine ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement

Burlet, H.

Cutrona, J.

Zahm, J. M.

Birembaut, P.

Nawrocki-Raby, B.

Language :

English

Title :

Fhit regulates invasion of lung tumor cells

Publication date :

2010

Journal title :

Oncogene

ISSN :

0950-9232

eISSN :

1476-5594

Publisher :

Nature Publishing Group, Basingstoke, United Kingdom

Volume :

Issue :

Pages :

1203-13

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 22 June 2010

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Bibliography

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