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

doi:10.1016/j.imbio.2012.01.001

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

Research output: Contribution to journal › Article › peer-review

37 Citations (Scopus)

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.

Original language	English
Pages (from-to)	926-934
Number of pages	9
Journal	Immunobiology
Volume	217
Issue number	9
DOIs	https://doi.org/10.1016/j.imbio.2012.01.001
Publication status	Published - 2012 Sept

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology
Hematology

Access to Document

10.1016/j.imbio.2012.01.001

Cite this

@article{4df539e8fc6b4ca6ae32b9bd951af77c,

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.",

author = "Tseng, \{Po Chun\} and Huang, \{Wei Ching\} and Chen, \{Chia Ling\} and Sheu, \{Bor Shyang\} and Shan, \{Yan Shen\} and Tsai, \{Cheng Chieh\} and Wang, \{Chi Yun\} and Chen, \{Su O.\} and Hsieh, \{Chia Yuan\} and Lin, \{Chiou Feng\}",

note = "Funding Information: We thank the Immunobiology Core, Research Center of Clinical Medicine, National Cheng Kung University Hospital, for providing services that include training, technical support, and assistance with experimental design and data analysis using Flow Cytometry Core facilities. We thank Huey-Kang Sytwu, MD, PhD (Graduate Institute of Life Science, National Defense Medical Center, Taiwan) for materials and for assistance with lentiviral-based shRNA experiments. This work was supported by grant NHRI-EX99-9917NC from the National Health Research Institutes, Taiwan . ",

year = "2012",

month = sep,

doi = "10.1016/j.imbio.2012.01.001",

language = "English",

volume = "217",

pages = "926--934",

journal = "Immunobiology",

issn = "0171-2985",

publisher = "Elsevier GmbH",

number = "9",

}

TY - JOUR

T1 - Regulation of SHP2 by PTEN/AKT/GSK-3β signaling facilitates IFN-γ resistance in hyperproliferating gastric cancer

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

N1 - Funding Information: We thank the Immunobiology Core, Research Center of Clinical Medicine, National Cheng Kung University Hospital, for providing services that include training, technical support, and assistance with experimental design and data analysis using Flow Cytometry Core facilities. We thank Huey-Kang Sytwu, MD, PhD (Graduate Institute of Life Science, National Defense Medical Center, Taiwan) for materials and for assistance with lentiviral-based shRNA experiments. This work was supported by grant NHRI-EX99-9917NC from the National Health Research Institutes, Taiwan .

PY - 2012/9

Y1 - 2012/9

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.

UR - https://www.scopus.com/pages/publications/84864303844

UR - https://www.scopus.com/pages/publications/84864303844#tab=citedBy

U2 - 10.1016/j.imbio.2012.01.001

DO - 10.1016/j.imbio.2012.01.001

M3 - Article

C2 - 22325465

AN - SCOPUS:84864303844

SN - 0171-2985

VL - 217

SP - 926

EP - 934

JO - Immunobiology

JF - Immunobiology

IS - 9

ER -

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

Abstract

UN SDGs

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this