Abstract
Background: Increased activity or expression of integrin-linked kinase (ILK), which regulates cell adhesion, migration, and proliferation, leads to oncogenesis. We identified the molecular basis for the regulation of ILK and its alternative role in conferring ERK1/2/NF-κB-mediated growth advantages to gastric cancer cells. Results: Inhibiting ILK with short hairpin RNA or T315, a putative ILK inhibitor, abolished NF-κB-mediated the growth in the human gastric cancer cells AGS, SNU-1, MKN45, and GES-1. ILK stimulated Ras activity to activate the c-Raf/MEK1/2/ERK1/2/ribosomal S6 kinase/inhibitor of κBa/NF-κB signaling by facilitating the formation of the IQ motif-containing GTPase-activating protein 1 (IQGAP1)-Ras complex. Forced enzymatic ILK expression promoted cell growth by facilitating ERK1/2/NF-κB signaling. PI3K activation or decreased PTEN expression prolonged ERK1/2 activation by protecting ILK from proteasome-mediated degradation. C-terminus of heat shock cognate 70 interacting protein, an HSP90-associated E3 ubiquitin ligase, mediated ILK ubiquitination to control PI3K-and HSP90-regulated ILK stabilization and signaling. In addition to cell growth, the identified pathway promoted cell migration and reduced the sensitivity of gastric cancer cells to the anticancer agents 5-fluorouracil and cisplatin. Additionally, exogenous administration of EGF as well as overexpression of EGFR triggered ILK-and IQGAP1-regulated ERK1/2/NF-κB activation, cell growth, and migration. Conclusion: An increase in ILK non-canonically promotes ERK1/2/NF-κB activation and leads to the growth of gastric cancer cells.
| Original language | English |
|---|---|
| Article number | 69 |
| Journal | Cell Communication and Signaling |
| Volume | 12 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2014 Jan 1 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Cell Biology
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An increase in integrin-linked kinase noncanonically confers NF-κB-mediated growth advantages to gastric cancer cells by activating ERK1/2. / Tseng, Po Chun; Chen, Chia Ling; Shan, Yan-Shen; Chang, Wen Teng; Liu, Hsiao-Sheng; Hong, Tse-Ming; Hsieh, Chia Yuan; Lin, Sheng-Hsiang; Lin, Chiou Feng.
In: Cell Communication and Signaling, Vol. 12, No. 1, 69, 01.01.2014.Research output: Contribution to journal › Article
TY - JOUR
T1 - An increase in integrin-linked kinase noncanonically confers NF-κB-mediated growth advantages to gastric cancer cells by activating ERK1/2
AU - Tseng, Po Chun
AU - Chen, Chia Ling
AU - Shan, Yan-Shen
AU - Chang, Wen Teng
AU - Liu, Hsiao-Sheng
AU - Hong, Tse-Ming
AU - Hsieh, Chia Yuan
AU - Lin, Sheng-Hsiang
AU - Lin, Chiou Feng
PY - 2014/1/1
Y1 - 2014/1/1
N2 - Background: Increased activity or expression of integrin-linked kinase (ILK), which regulates cell adhesion, migration, and proliferation, leads to oncogenesis. We identified the molecular basis for the regulation of ILK and its alternative role in conferring ERK1/2/NF-κB-mediated growth advantages to gastric cancer cells. Results: Inhibiting ILK with short hairpin RNA or T315, a putative ILK inhibitor, abolished NF-κB-mediated the growth in the human gastric cancer cells AGS, SNU-1, MKN45, and GES-1. ILK stimulated Ras activity to activate the c-Raf/MEK1/2/ERK1/2/ribosomal S6 kinase/inhibitor of κBa/NF-κB signaling by facilitating the formation of the IQ motif-containing GTPase-activating protein 1 (IQGAP1)-Ras complex. Forced enzymatic ILK expression promoted cell growth by facilitating ERK1/2/NF-κB signaling. PI3K activation or decreased PTEN expression prolonged ERK1/2 activation by protecting ILK from proteasome-mediated degradation. C-terminus of heat shock cognate 70 interacting protein, an HSP90-associated E3 ubiquitin ligase, mediated ILK ubiquitination to control PI3K-and HSP90-regulated ILK stabilization and signaling. In addition to cell growth, the identified pathway promoted cell migration and reduced the sensitivity of gastric cancer cells to the anticancer agents 5-fluorouracil and cisplatin. Additionally, exogenous administration of EGF as well as overexpression of EGFR triggered ILK-and IQGAP1-regulated ERK1/2/NF-κB activation, cell growth, and migration. Conclusion: An increase in ILK non-canonically promotes ERK1/2/NF-κB activation and leads to the growth of gastric cancer cells.
AB - Background: Increased activity or expression of integrin-linked kinase (ILK), which regulates cell adhesion, migration, and proliferation, leads to oncogenesis. We identified the molecular basis for the regulation of ILK and its alternative role in conferring ERK1/2/NF-κB-mediated growth advantages to gastric cancer cells. Results: Inhibiting ILK with short hairpin RNA or T315, a putative ILK inhibitor, abolished NF-κB-mediated the growth in the human gastric cancer cells AGS, SNU-1, MKN45, and GES-1. ILK stimulated Ras activity to activate the c-Raf/MEK1/2/ERK1/2/ribosomal S6 kinase/inhibitor of κBa/NF-κB signaling by facilitating the formation of the IQ motif-containing GTPase-activating protein 1 (IQGAP1)-Ras complex. Forced enzymatic ILK expression promoted cell growth by facilitating ERK1/2/NF-κB signaling. PI3K activation or decreased PTEN expression prolonged ERK1/2 activation by protecting ILK from proteasome-mediated degradation. C-terminus of heat shock cognate 70 interacting protein, an HSP90-associated E3 ubiquitin ligase, mediated ILK ubiquitination to control PI3K-and HSP90-regulated ILK stabilization and signaling. In addition to cell growth, the identified pathway promoted cell migration and reduced the sensitivity of gastric cancer cells to the anticancer agents 5-fluorouracil and cisplatin. Additionally, exogenous administration of EGF as well as overexpression of EGFR triggered ILK-and IQGAP1-regulated ERK1/2/NF-κB activation, cell growth, and migration. Conclusion: An increase in ILK non-canonically promotes ERK1/2/NF-κB activation and leads to the growth of gastric cancer cells.
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U2 - 10.1186/s12964-014-0069-3
DO - 10.1186/s12964-014-0069-3
M3 - Article
VL - 12
JO - Cell Communication and Signaling
JF - Cell Communication and Signaling
SN - 1478-811X
IS - 1
M1 - 69
ER -