Regulation of SHP2 by PTEN/AKT/GSK-3β signaling facilitates IFN-γ resistance in hyperproliferating gastric cancer

Po-Chun Tseng, Wei-Ching Huang, Chia-Ling Chen, Bor-Shyang Sheu, Yan-Shen Shan, Cheng-Chieh Tsai, Chi-Yun Wang, Su-O. Chen, Chia-Yuan Hsieh, Chiou Feng Lin

研究成果: 雜誌貢獻文章

27 引文 (Scopus)

摘要

Oncogenic activation accompanied by escape from immune surveillance, such as IFN-γ resistance, is critical for cancer cell growth and survival. In this study, we investigated the crosstalk signaling between IFN-γ resistance and signaling of hyperproliferation in gastric cancer cells. IFN-γ inhibited the cell growth of MKN45 cells but not hyperproliferating AGS cells. AGS cells did not respond to IFN-γ because of a decrease in STAT1 but not due to dysfunctional IFN-γ receptors. Signaling of PI3K/AKT, as well as MEK/ERK, was required for the hyperproliferation; notably, PI3K/AKT alone mediated the IFN-γ resistance. Aberrant Src homology-2 domain-containing phosphatase (SHP) 2 determined IFN-γ resistance but unexpectedly had no effects on hyperproliferation or ERK activation. In the IFN-γ resistant cells, inactivation of glycogen synthase kinase (GSK)-3β by PI3K/AKT was important for SHP2 activation but not for hyperproliferation. An imbalance of AKT/GSK-3β/SHP2 caused by a reduction of PTEN was important for the crosstalk between IFN-γ resistance and hyperproliferation. PI3K is constitutively expressed in AGS cells and immunohistochemical staining showed a correlation between hyperproliferation and expression of SHP2 and STAT1 in gastric tumors. These results demonstrate the effects of PTEN/AKT/GSK-3β/SHP2 signaling on IFN-γ resistance in hyperproliferating gastric cancer cells.
原文英語
頁(從 - 到)926-934
頁數9
期刊Immunobiology
217
發行號9
DOIs
出版狀態已發佈 - 九月 2012
對外發佈Yes

指紋

Glycogen Synthase Kinase 3
Stomach Neoplasms
Phosphatidylinositol 3-Kinases
SH2 Domain-Containing Protein Tyrosine Phosphatases
Mitogen-Activated Protein Kinase Kinases
Growth
Neoplasms
Cell Survival
Stomach
Staining and Labeling

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Hematology

引用此文

Regulation of SHP2 by PTEN/AKT/GSK-3β signaling facilitates IFN-γ resistance in hyperproliferating gastric cancer. / Tseng, Po-Chun; Huang, Wei-Ching; Chen, Chia-Ling; Sheu, Bor-Shyang; Shan, Yan-Shen; Tsai, Cheng-Chieh; Wang, Chi-Yun; Chen, Su-O.; Hsieh, Chia-Yuan; Lin, Chiou Feng.

於: Immunobiology, 卷 217, 編號 9, 09.2012, p. 926-934.

研究成果: 雜誌貢獻文章

Tseng, Po-Chun ; Huang, Wei-Ching ; Chen, Chia-Ling ; Sheu, Bor-Shyang ; Shan, Yan-Shen ; Tsai, Cheng-Chieh ; Wang, Chi-Yun ; Chen, Su-O. ; Hsieh, Chia-Yuan ; Lin, Chiou Feng. / Regulation of SHP2 by PTEN/AKT/GSK-3β signaling facilitates IFN-γ resistance in hyperproliferating gastric cancer. 於: Immunobiology. 2012 ; 卷 217, 編號 9. 頁 926-934.
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title = "Regulation of SHP2 by PTEN/AKT/GSK-3β signaling facilitates IFN-γ resistance in hyperproliferating gastric cancer",
abstract = "Oncogenic activation accompanied by escape from immune surveillance, such as IFN-γ resistance, is critical for cancer cell growth and survival. In this study, we investigated the crosstalk signaling between IFN-γ resistance and signaling of hyperproliferation in gastric cancer cells. IFN-γ inhibited the cell growth of MKN45 cells but not hyperproliferating AGS cells. AGS cells did not respond to IFN-γ because of a decrease in STAT1 but not due to dysfunctional IFN-γ receptors. Signaling of PI3K/AKT, as well as MEK/ERK, was required for the hyperproliferation; notably, PI3K/AKT alone mediated the IFN-γ resistance. Aberrant Src homology-2 domain-containing phosphatase (SHP) 2 determined IFN-γ resistance but unexpectedly had no effects on hyperproliferation or ERK activation. In the IFN-γ resistant cells, inactivation of glycogen synthase kinase (GSK)-3β by PI3K/AKT was important for SHP2 activation but not for hyperproliferation. An imbalance of AKT/GSK-3β/SHP2 caused by a reduction of PTEN was important for the crosstalk between IFN-γ resistance and hyperproliferation. PI3K is constitutively expressed in AGS cells and immunohistochemical staining showed a correlation between hyperproliferation and expression of SHP2 and STAT1 in gastric tumors. These results demonstrate the effects of PTEN/AKT/GSK-3β/SHP2 signaling on IFN-γ resistance in hyperproliferating gastric cancer cells.",
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author = "Po-Chun Tseng and Wei-Ching Huang and Chia-Ling Chen and Bor-Shyang Sheu and Yan-Shen Shan and Cheng-Chieh Tsai and Chi-Yun Wang and Su-O. Chen and Chia-Yuan Hsieh and Lin, {Chiou Feng}",
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AU - Tseng, Po-Chun

AU - Huang, Wei-Ching

AU - Chen, Chia-Ling

AU - Sheu, Bor-Shyang

AU - Shan, Yan-Shen

AU - Tsai, Cheng-Chieh

AU - Wang, Chi-Yun

AU - Chen, Su-O.

AU - Hsieh, Chia-Yuan

AU - Lin, Chiou Feng

PY - 2012/9

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N2 - Oncogenic activation accompanied by escape from immune surveillance, such as IFN-γ resistance, is critical for cancer cell growth and survival. In this study, we investigated the crosstalk signaling between IFN-γ resistance and signaling of hyperproliferation in gastric cancer cells. IFN-γ inhibited the cell growth of MKN45 cells but not hyperproliferating AGS cells. AGS cells did not respond to IFN-γ because of a decrease in STAT1 but not due to dysfunctional IFN-γ receptors. Signaling of PI3K/AKT, as well as MEK/ERK, was required for the hyperproliferation; notably, PI3K/AKT alone mediated the IFN-γ resistance. Aberrant Src homology-2 domain-containing phosphatase (SHP) 2 determined IFN-γ resistance but unexpectedly had no effects on hyperproliferation or ERK activation. In the IFN-γ resistant cells, inactivation of glycogen synthase kinase (GSK)-3β by PI3K/AKT was important for SHP2 activation but not for hyperproliferation. An imbalance of AKT/GSK-3β/SHP2 caused by a reduction of PTEN was important for the crosstalk between IFN-γ resistance and hyperproliferation. PI3K is constitutively expressed in AGS cells and immunohistochemical staining showed a correlation between hyperproliferation and expression of SHP2 and STAT1 in gastric tumors. These results demonstrate the effects of PTEN/AKT/GSK-3β/SHP2 signaling on IFN-γ resistance in hyperproliferating gastric cancer cells.

AB - Oncogenic activation accompanied by escape from immune surveillance, such as IFN-γ resistance, is critical for cancer cell growth and survival. In this study, we investigated the crosstalk signaling between IFN-γ resistance and signaling of hyperproliferation in gastric cancer cells. IFN-γ inhibited the cell growth of MKN45 cells but not hyperproliferating AGS cells. AGS cells did not respond to IFN-γ because of a decrease in STAT1 but not due to dysfunctional IFN-γ receptors. Signaling of PI3K/AKT, as well as MEK/ERK, was required for the hyperproliferation; notably, PI3K/AKT alone mediated the IFN-γ resistance. Aberrant Src homology-2 domain-containing phosphatase (SHP) 2 determined IFN-γ resistance but unexpectedly had no effects on hyperproliferation or ERK activation. In the IFN-γ resistant cells, inactivation of glycogen synthase kinase (GSK)-3β by PI3K/AKT was important for SHP2 activation but not for hyperproliferation. An imbalance of AKT/GSK-3β/SHP2 caused by a reduction of PTEN was important for the crosstalk between IFN-γ resistance and hyperproliferation. PI3K is constitutively expressed in AGS cells and immunohistochemical staining showed a correlation between hyperproliferation and expression of SHP2 and STAT1 in gastric tumors. These results demonstrate the effects of PTEN/AKT/GSK-3β/SHP2 signaling on IFN-γ resistance in hyperproliferating gastric cancer cells.

KW - AKT

KW - Gastric cancer

KW - GSK-3β

KW - Hyperproliferation

KW - IFN-γ

KW - PTEN

KW - SHP2

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