title: Suppression of anoikis by v-Src but not by activated c-H-ras in human gallbladder epithelial cells.
abstract: Detachment of anchorage-dependent normal epithelial cells from their substratum causes the type of apoptosis known as anoikis, whereas malignant cells can proliferate independently of anchorage. Because src and ras oncogenes are activated in many human cancers, we investigated their role and downstream signaling pathways in anoikis resistance, using HAG-1 human epithelial cells transfected with v-src or activated H-ras. Consequently, anchorage-dependent mock- or ras-transfected cells underwent anoikis. In contrast, anchorage-independent v-Src-transformed cells did not exhibit such apoptotic features. Focal adhesion kinase (FAK), a transducer of integrin, was only activated in v-Src-transformed cells. Herbimycin A, an Src kinase inhibitor, reduced tyrosyl phosphorylation of FAK and reversed resistance to anoikis. However, both protein kinase C (PKC) and phophatidylinositol-3 (PI-3) kinase inhibitors failed to induce anoikis. These data suggest that the ability of activated Src to prevent anoikis may be mediated by Src to a downstream signaling pathway involving FAK, but not Ras, PI-3 kinase, or PKC.
authors.affiliation: First Department of Internal Medicine and Department of Medicine and Biosystemic Science, Graduate School of Medicine, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan.
authors.forename: Chizuko
authors.initials: C
authors.lastname: Hisano
authors.forename: Risa
authors.initials: R
authors.lastname: Tanaka
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Fujishima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ariyama
authors.forename: Tanji
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: Takashi
authors.initials: T
authors.lastname: Tatsumoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Mitsugi
authors.forename: Minoru
authors.initials: M
authors.lastname: Nakamura
authors.forename: Shuji
authors.initials: S
authors.lastname: Nakano
mesh_terms: D023102:Anoikis / Q000235:genetics*; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D011905:Genes, ras / Q000235:genetics / Q000502:physiology; D016391:Genes, src / Q000235:genetics / Q000502:physiology*; D006801:Humans
chemical_list: D004791:Enzyme Inhibitors