Article (Scientific journals)
Fhit regulates EMT targets through an EGFR/Src/ERK/Slug signaling axis in human bronchial cells.
Joannes, Audrey; Grelet, Simon; Duca, Laurent et al.
2014In Molecular Cancer Research, 12 (5), p. 775-83
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Abstract :
[en] In many cancers, including lung carcinomas, Fragile histidine triad (Fhit) is frequently decreased or lost. Fhit status has recently been shown to be associated with elevated in vitro and in vivo invasiveness in lung cancer. Tumor cell invasion is facilitated by epithelial-mesenchymal transition (EMT), a process by which tumor cells lose their epithelial features to acquire a mesenchymal cell-like phenotype. In this study, the mechanism underlying Fhit-regulated EMT was deciphered. Using Slug knockdown, pharmacologic inhibitors PD98059, PP1, and gefitinib as well as an anti-EGFR antibody, it was demonstrated that Fhit silencing in bronchial cells induced overexpression of two primary EMT-associated targets, MMP-9 and vimentin, to regulate cell invasion dependent on an EGFR/Src/ERK/Slug signaling pathway. Moreover, ectopic expression of Fhit in Fhit-deficient lung cancer cells downregulated this pathway. Finally, an inverse correlation was observed between Fhit and phospho-EGFR levels in a cohort of human squamous cell lung carcinoma specimens. These results demonstrate a Fhit-dependent mechanism in the control of EMT-regulated EGFR signaling. IMPLICATIONS: This study adds new insight into the regulatory mechanism of EMT, a process known to increase resistance to conventional and targeted therapies in lung cancer.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Joannes, Audrey
Grelet, Simon
Duca, Laurent
Gilles, Christine ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Kileztky, Claire
Dalstein, Veronique
Birembaut, Philippe
Polette, Myriam
Nawrocki-Raby, Beatrice
Language :
English
Title :
Fhit regulates EMT targets through an EGFR/Src/ERK/Slug signaling axis in human bronchial cells.
Publication date :
2014
Journal title :
Molecular Cancer Research
ISSN :
1541-7786
eISSN :
1557-3125
Publisher :
American Association for Cancer Research, Inc. (AACR)
Volume :
12
Issue :
5
Pages :
775-83
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
(c)2014 AACR.
Available on ORBi :
since 08 September 2014

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