title: Integrin α5β1 simultaneously controls EGFR-dependent proliferation and Akt-dependent pro-survival signaling in epidermoid carcinoma cells.
abstract: To delineate distinctive role of the components of α5β1 integrin-EGFR axis in control of epidermoid carcinoma cell proliferation, we performed individual inhibition of α5β1 and EGFR via genetic and phamacological methods, respectively. We demonstrated that pharmacological inhibition of epidermal growth factor receptor (EGFR) significantly affected proliferation of A431 human cells by inducing the G0/G1 cell cycle arrest, whereas shRNA-mediated depletion of α5 subunit of α5β1 integrin led to a similar type of cell cycle arrest followed by significant apoptosis. Both treatments resulted in suppression of activated (phosphorylated) forms of focal adhesion kinase (FAK) and Erk. However, unlike EGFR inhibition, depletion of α5 led to substantial suppression of AKT activity. Accordingly, pharmacological inhibition of EGFR and AKT recapitulated detrimental effects caused by shRNA-mediated depletion of α5. Moreover, depletion of α5 led to a severe drop in the amounts of active EGFR. Thus, for the first time, we demonstrated that α5β1 integrin simultaneously maintains pro-survival signaling via continuous activation of AKT and up-regulates proliferation via activation of EGFR.
authors.affiliation: V.N. Orekhovich Institute of Biomedical Chemistry RAMS, Moscow, Russia.
authors.forename: Galina E
authors.initials: GE
authors.lastname: Morozevich
authors.forename: Nadezda I
authors.initials: NI
authors.lastname: Kozlova
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Ushakova
authors.forename: Marina E
authors.initials: ME
authors.lastname: Preobrazhenskaya
authors.forename: Albert E
authors.initials: AE
authors.lastname: Berman
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D039081:Integrin alpha5beta1; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt