Suppression of anoikis by v-Src but not by activated c-H-Ras in human gallbladder epithelial cells

Chizuko Hisano, Risa Tanaka, Hiromitsu Fujishima, hiroshi ariyama, Tanji Tsuchiya, Takashi Tatsumoto, Kenji Mitsugi, Minoru Nakamura, Shuji Nakano

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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.

Original languageEnglish
Pages (from-to)415-421
Number of pages7
JournalCell Biology International
Volume27
Issue number5
DOIs
Publication statusPublished - May 1 2003

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Anoikis
Gallbladder
Epithelial Cells
Focal Adhesion Protein-Tyrosine Kinases
src Genes
ras Genes
src-Family Kinases
Transducers
Integrins
Protein Kinase C
Phosphotransferases
Phosphorylation
Apoptosis

All Science Journal Classification (ASJC) codes

  • Cell Biology

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Suppression of anoikis by v-Src but not by activated c-H-Ras in human gallbladder epithelial cells. / Hisano, Chizuko; Tanaka, Risa; Fujishima, Hiromitsu; ariyama, hiroshi; Tsuchiya, Tanji; Tatsumoto, Takashi; Mitsugi, Kenji; Nakamura, Minoru; Nakano, Shuji.

In: Cell Biology International, Vol. 27, No. 5, 01.05.2003, p. 415-421.

Research output: Contribution to journalArticle

Hisano, C, Tanaka, R, Fujishima, H, ariyama, H, Tsuchiya, T, Tatsumoto, T, Mitsugi, K, Nakamura, M & Nakano, S 2003, 'Suppression of anoikis by v-Src but not by activated c-H-Ras in human gallbladder epithelial cells', Cell Biology International, vol. 27, no. 5, pp. 415-421. https://doi.org/10.1016/S1065-6995(03)00032-5
Hisano, Chizuko ; Tanaka, Risa ; Fujishima, Hiromitsu ; ariyama, hiroshi ; Tsuchiya, Tanji ; Tatsumoto, Takashi ; Mitsugi, Kenji ; Nakamura, Minoru ; Nakano, Shuji. / Suppression of anoikis by v-Src but not by activated c-H-Ras in human gallbladder epithelial cells. In: Cell Biology International. 2003 ; Vol. 27, No. 5. pp. 415-421.
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