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 language | English |
|---|---|
| Pages (from-to) | 415-421 |
| Number of pages | 7 |
| Journal | Cell Biology International |
| Volume | 27 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 1 2003 |
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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 journal › Article
}
TY - JOUR
T1 - Suppression of anoikis by v-Src but not by activated c-H-Ras in human gallbladder epithelial cells
AU - Hisano, Chizuko
AU - Tanaka, Risa
AU - Fujishima, Hiromitsu
AU - Ariyama, Hiroshi
AU - Tsuchiya, Tanji
AU - Tatsumoto, Takashi
AU - Mitsugi, Kenji
AU - Nakamura, Minoru
AU - Nakano, Shuji
PY - 2003/5/1
Y1 - 2003/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0642306275&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0642306275&partnerID=8YFLogxK
U2 - 10.1016/S1065-6995(03)00032-5
DO - 10.1016/S1065-6995(03)00032-5
M3 - Article
C2 - 12758089
AN - SCOPUS:0642306275
VL - 27
SP - 415
EP - 421
JO - Cell Biology International
JF - Cell Biology International
SN - 1065-6995
IS - 5
ER -