ER stress‐related ATF6 upregulates CIP2A and contributes to poor prognosis of colon cancer
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. Cancero...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-10-01
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| Series: | Molecular Oncology |
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| Online Access: | https://doi.org/10.1002/1878-0261.12365 |
| _version_ | 1829100551432830976 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Chun‐Yu Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T22:34:59Z |
| format | Article |
| id | doaj.art-1010005a356949b49f7c49abb67ad80d |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-12-10T22:34:59Z |
| publishDate | 2018-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-1010005a356949b49f7c49abb67ad80d2022-12-22T01:30:56ZengWileyMolecular Oncology1574-78911878-02612018-10-0112101706171710.1002/1878-0261.12365ER stress‐related ATF6 upregulates CIP2A and contributes to poor prognosis of colon cancerChun‐Yu Liu0Chia‐Chi Hsu1Tzu‐Ting Huang2Chia‐Han Lee3Ji‐Lin Chen4Shung‐Haur Yang5Jeng‐Kai Jiang6Wei‐Shone Chen7Kuan‐Der Lee8Hao‐Wei Teng9Division of Medical Oncology Department of Oncology Center for Immuno‐Oncology Taipei Veterans General Hospital TaiwanDivision of Medical Oncology Department of Oncology Center for Immuno‐Oncology Taipei Veterans General Hospital TaiwanDivision of Medical Oncology Department of Oncology Center for Immuno‐Oncology Taipei Veterans General Hospital TaiwanDivision of Medical Oncology Department of Oncology Center for Immuno‐Oncology Taipei Veterans General Hospital TaiwanDivision of Medical Oncology Department of Oncology Center for Immuno‐Oncology Taipei Veterans General Hospital TaiwanSchool of Medicine National Yang‐Ming University Taipei TaiwanSchool of Medicine National Yang‐Ming University Taipei TaiwanSchool of Medicine National Yang‐Ming University Taipei TaiwanDivision of Hematology and Oncology Department of Internal Medicine Taipei Medical University Hospital TaiwanDivision of Medical Oncology Department of Oncology Center for Immuno‐Oncology Taipei Veterans General Hospital TaiwanEndoplasmic 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.https://doi.org/10.1002/1878-0261.12365ATF6CIP2Acolon cancerER stress |
| spellingShingle | 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 ER stress‐related ATF6 upregulates CIP2A and contributes to poor prognosis of colon cancer Molecular Oncology ATF6 CIP2A colon cancer ER stress |
| title | ER stress‐related ATF6 upregulates CIP2A and contributes to poor prognosis of colon cancer |
| title_full | ER stress‐related ATF6 upregulates CIP2A and contributes to poor prognosis of colon cancer |
| title_fullStr | ER stress‐related ATF6 upregulates CIP2A and contributes to poor prognosis of colon cancer |
| title_full_unstemmed | ER stress‐related ATF6 upregulates CIP2A and contributes to poor prognosis of colon cancer |
| title_short | ER stress‐related ATF6 upregulates CIP2A and contributes to poor prognosis of colon cancer |
| title_sort | er stress related atf6 upregulates cip2a and contributes to poor prognosis of colon cancer |
| topic | ATF6 CIP2A colon cancer ER stress |
| url | https://doi.org/10.1002/1878-0261.12365 |
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