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Suppression of anoikis by v‐Src but not by activated c‐H‐Ras in human gallbladder epithelial cells
Author(s) -
Hisano Chizuko,
Tanaka Risa,
Fujishima Hiromitsu,
Ariyama Hiroshi,
Tsuchiya Tanji,
Tatsumoto Takashi,
Mitsugi Kenji,
Nakamura Minoru,
Nakano Shuji
Publication year - 2003
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/s1065-6995(03)00032-5
Subject(s) - anoikis , proto oncogene tyrosine protein kinase src , focal adhesion , microbiology and biotechnology , kinase , transfection , cancer research , chemistry , biology , signal transduction , apoptosis , cell culture , programmed cell death , biochemistry , genetics
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.