ER stress-related ATF6 upregulates CIP2A and contributes to poor prognosis of colon cancer

Chun Yu Liu, Chia Chi Hsu, Tzu Ting Huang, Chia Han Lee, Ji Lin Chen, Shung Haur Yang, Jeng Kai Jiang, Wei Shone Chen, Kuan Der Lee, Hao Wei Teng

研究成果: 雜誌貢獻文章

2 引文 (Scopus)

摘要

Endoplasmic reticulum (ER) stress is an adaptive response to various stress conditions and plays emerging roles in cancer. Activating transcription factor 6 (ATF6), one of the three major ER stress transducers, has been shown to contribute to chemoresistance by altering cancer cell survival. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogene, and its expression has been correlated with the prognosis of patients with cancer. In this study, we aimed to explore the relationship between ER stress-related ATF signaling and CIP2A. We found that CIP2A expression was positively correlated with ATF6 expression by analyzing publicly available RNA sequence data of patients with colorectal cancer (The Cancer Genome Atlas, TCGA). In addition, we demonstrated that tunicamycin-induced ER stress in vitro upregulated ATF6 and CIP2A. Mechanistically, we found that ATF6 directly bound to the CIP2A promoter and induced CIP2A gene expression, which contributed to colon cancer cell survival. Furthermore, knockdown of CIP2A reduced the viability of cells under ER stress. Most importantly, immunohistochemical analysis of a tissue microarray from a colon cancer patient cohort showed that higher expression levels of ATF6 and CIP2A were associated with a trend toward poor prognosis. Taken together, our results show that ER stress-related ATF6 upregulates CIP2A and contributes to the prognosis of colon cancer. Targeting CIP2A may disrupt ER stress-mediated colon cancer cell survival and thus improve the prognosis of patients with colon cancer.

原文英語
頁(從 - 到)1706-1717
頁數12
期刊Molecular Oncology
12
發行號10
DOIs
出版狀態已發佈 - 十月 1 2018

指紋

Activating Transcription Factor 6
Protein Phosphatase 2
Endoplasmic Reticulum Stress
Colonic Neoplasms
Up-Regulation
Cell Survival
Neoplasms
Tissue Array Analysis
Tunicamycin
Atlases
Transducers
Oncogenes
Colorectal Neoplasms

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Oncology
  • Cancer Research

引用此文

Liu, C. Y., Hsu, C. C., Huang, T. T., Lee, C. H., Chen, J. L., Yang, S. H., ... Teng, H. W. (2018). ER stress-related ATF6 upregulates CIP2A and contributes to poor prognosis of colon cancer. Molecular Oncology, 12(10), 1706-1717. https://doi.org/10.1002/1878-0261.12365

ER stress-related ATF6 upregulates CIP2A and contributes to poor prognosis of colon cancer. / Liu, Chun Yu; Hsu, Chia Chi; Huang, Tzu Ting; Lee, Chia Han; Chen, Ji Lin; Yang, Shung Haur; Jiang, Jeng Kai; Chen, Wei Shone; Lee, Kuan Der; Teng, Hao Wei.

於: Molecular Oncology, 卷 12, 編號 10, 01.10.2018, p. 1706-1717.

研究成果: 雜誌貢獻文章

Liu, CY, Hsu, CC, Huang, TT, Lee, CH, Chen, JL, Yang, SH, Jiang, JK, Chen, WS, Lee, KD & Teng, HW 2018, 'ER stress-related ATF6 upregulates CIP2A and contributes to poor prognosis of colon cancer', Molecular Oncology, 卷 12, 編號 10, 頁 1706-1717. https://doi.org/10.1002/1878-0261.12365
Liu, Chun Yu ; Hsu, Chia Chi ; Huang, Tzu Ting ; Lee, Chia Han ; Chen, Ji Lin ; Yang, Shung Haur ; Jiang, Jeng Kai ; Chen, Wei Shone ; Lee, Kuan Der ; Teng, Hao Wei. / ER stress-related ATF6 upregulates CIP2A and contributes to poor prognosis of colon cancer. 於: Molecular Oncology. 2018 ; 卷 12, 編號 10. 頁 1706-1717.
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abstract = "Endoplasmic reticulum (ER) stress is an adaptive response to various stress conditions and plays emerging roles in cancer. Activating transcription factor 6 (ATF6), one of the three major ER stress transducers, has been shown to contribute to chemoresistance by altering cancer cell survival. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogene, and its expression has been correlated with the prognosis of patients with cancer. In this study, we aimed to explore the relationship between ER stress-related ATF signaling and CIP2A. We found that CIP2A expression was positively correlated with ATF6 expression by analyzing publicly available RNA sequence data of patients with colorectal cancer (The Cancer Genome Atlas, TCGA). In addition, we demonstrated that tunicamycin-induced ER stress in vitro upregulated ATF6 and CIP2A. Mechanistically, we found that ATF6 directly bound to the CIP2A promoter and induced CIP2A gene expression, which contributed to colon cancer cell survival. Furthermore, knockdown of CIP2A reduced the viability of cells under ER stress. Most importantly, immunohistochemical analysis of a tissue microarray from a colon cancer patient cohort showed that higher expression levels of ATF6 and CIP2A were associated with a trend toward poor prognosis. Taken together, our results show that ER stress-related ATF6 upregulates CIP2A and contributes to the prognosis of colon cancer. Targeting CIP2A may disrupt ER stress-mediated colon cancer cell survival and thus improve the prognosis of patients with colon cancer.",
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AU - Liu, Chun Yu

AU - Hsu, Chia Chi

AU - Huang, Tzu Ting

AU - Lee, Chia Han

AU - Chen, Ji Lin

AU - Yang, Shung Haur

AU - Jiang, Jeng Kai

AU - Chen, Wei Shone

AU - Lee, Kuan Der

AU - Teng, Hao Wei

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Y1 - 2018/10/1

N2 - Endoplasmic reticulum (ER) stress is an adaptive response to various stress conditions and plays emerging roles in cancer. Activating transcription factor 6 (ATF6), one of the three major ER stress transducers, has been shown to contribute to chemoresistance by altering cancer cell survival. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogene, and its expression has been correlated with the prognosis of patients with cancer. In this study, we aimed to explore the relationship between ER stress-related ATF signaling and CIP2A. We found that CIP2A expression was positively correlated with ATF6 expression by analyzing publicly available RNA sequence data of patients with colorectal cancer (The Cancer Genome Atlas, TCGA). In addition, we demonstrated that tunicamycin-induced ER stress in vitro upregulated ATF6 and CIP2A. Mechanistically, we found that ATF6 directly bound to the CIP2A promoter and induced CIP2A gene expression, which contributed to colon cancer cell survival. Furthermore, knockdown of CIP2A reduced the viability of cells under ER stress. Most importantly, immunohistochemical analysis of a tissue microarray from a colon cancer patient cohort showed that higher expression levels of ATF6 and CIP2A were associated with a trend toward poor prognosis. Taken together, our results show that ER stress-related ATF6 upregulates CIP2A and contributes to the prognosis of colon cancer. Targeting CIP2A may disrupt ER stress-mediated colon cancer cell survival and thus improve the prognosis of patients with colon cancer.

AB - Endoplasmic reticulum (ER) stress is an adaptive response to various stress conditions and plays emerging roles in cancer. Activating transcription factor 6 (ATF6), one of the three major ER stress transducers, has been shown to contribute to chemoresistance by altering cancer cell survival. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogene, and its expression has been correlated with the prognosis of patients with cancer. In this study, we aimed to explore the relationship between ER stress-related ATF signaling and CIP2A. We found that CIP2A expression was positively correlated with ATF6 expression by analyzing publicly available RNA sequence data of patients with colorectal cancer (The Cancer Genome Atlas, TCGA). In addition, we demonstrated that tunicamycin-induced ER stress in vitro upregulated ATF6 and CIP2A. Mechanistically, we found that ATF6 directly bound to the CIP2A promoter and induced CIP2A gene expression, which contributed to colon cancer cell survival. Furthermore, knockdown of CIP2A reduced the viability of cells under ER stress. Most importantly, immunohistochemical analysis of a tissue microarray from a colon cancer patient cohort showed that higher expression levels of ATF6 and CIP2A were associated with a trend toward poor prognosis. Taken together, our results show that ER stress-related ATF6 upregulates CIP2A and contributes to the prognosis of colon cancer. Targeting CIP2A may disrupt ER stress-mediated colon cancer cell survival and thus improve the prognosis of patients with colon cancer.

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