CPT1A promotes anoikis resistance in esophageal squamous cell carcinoma via redox homeostasis
Anoikis resistance was a prominent hallmark of cancer metastasis, and lipo-genic characteristics have been identified as another metabolic alteration during tumorigenesis. However, their crosstalk has not been fully elucidated, especially in advanced esophageal squamous cell carcinoma (ESCC). In thi...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231722003160 |
| _version_ | 1828118296834080768 |
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| author | Tian Tian Yunxin Lu Jinfei Lin Miao Chen Huijuan Qiu Wancui Zhu Haohui Sun Jinsheng Huang Han Yang Wuguo Deng |
| author_facet | Tian Tian Yunxin Lu Jinfei Lin Miao Chen Huijuan Qiu Wancui Zhu Haohui Sun Jinsheng Huang Han Yang Wuguo Deng |
| author_sort | Tian Tian |
| collection | DOAJ |
| description | Anoikis resistance was a prominent hallmark of cancer metastasis, and lipo-genic characteristics have been identified as another metabolic alteration during tumorigenesis. However, their crosstalk has not been fully elucidated, especially in advanced esophageal squamous cell carcinoma (ESCC). In this study, we showed, for the first time, that the key enzyme carnitine O-palmitoyl transferase 1 (CPT1A), which is involved in fatty acid oxidation (FAO), was markedly upregulated in ESCC cells upon detached culture via a metabolism PCR array. Overexpression of CPT1A was associated with poor survival of ESCC patients and could protect ESCC cells from apoptosis via maintaining redox homeostasis through supply of GSH and NADPH. Mechanistically, detached culture conditions enhanced the expression of the transcription factor ETV4 and suppressed the expression of the ubiquitin enzyme RNF2, which were responsible for the elevated expression of CPT1A at the mRNA and protein levels, respectively. Moreover, genetic or pharmacologic disruption of CPT1A switched off the NADPH supply and therefore prevented the anchorage-independent growth of ESCC cells in vitro and lung metastases of xenografted tumor models in vivo. Collectively, our results provide novel insights into how ESCC cancer cells exploit metabolic switching to form distant metastases and some evidence for the link between anoikis and FAO. |
| first_indexed | 2024-04-11T13:29:51Z |
| format | Article |
| id | doaj.art-4d7a172af0034e859ae334d25175f5cf |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-11T13:29:51Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-4d7a172af0034e859ae334d25175f5cf2022-12-22T04:21:52ZengElsevierRedox Biology2213-23172022-12-0158102544CPT1A promotes anoikis resistance in esophageal squamous cell carcinoma via redox homeostasisTian Tian0Yunxin Lu1Jinfei Lin2Miao Chen3Huijuan Qiu4Wancui Zhu5Haohui Sun6Jinsheng Huang7Han Yang8Wuguo Deng9Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China; Department of Medical Biochemistry and Molecular Biology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China; Corresponding author. Sun Yat-Sen University Cancer center, Guangzhou, China.;Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China; Corresponding author. Sun Yat-Sen University Cancer center, Guangzhou, China.;Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China; Corresponding author. Sun Yat-Sen University Cancer center, Guangzhou, China.Anoikis resistance was a prominent hallmark of cancer metastasis, and lipo-genic characteristics have been identified as another metabolic alteration during tumorigenesis. However, their crosstalk has not been fully elucidated, especially in advanced esophageal squamous cell carcinoma (ESCC). In this study, we showed, for the first time, that the key enzyme carnitine O-palmitoyl transferase 1 (CPT1A), which is involved in fatty acid oxidation (FAO), was markedly upregulated in ESCC cells upon detached culture via a metabolism PCR array. Overexpression of CPT1A was associated with poor survival of ESCC patients and could protect ESCC cells from apoptosis via maintaining redox homeostasis through supply of GSH and NADPH. Mechanistically, detached culture conditions enhanced the expression of the transcription factor ETV4 and suppressed the expression of the ubiquitin enzyme RNF2, which were responsible for the elevated expression of CPT1A at the mRNA and protein levels, respectively. Moreover, genetic or pharmacologic disruption of CPT1A switched off the NADPH supply and therefore prevented the anchorage-independent growth of ESCC cells in vitro and lung metastases of xenografted tumor models in vivo. Collectively, our results provide novel insights into how ESCC cancer cells exploit metabolic switching to form distant metastases and some evidence for the link between anoikis and FAO.http://www.sciencedirect.com/science/article/pii/S2213231722003160CPT1AFatty acid oxidationAnoikis resistanceEsophageal squamous cell carcinoma |
| spellingShingle | Tian Tian Yunxin Lu Jinfei Lin Miao Chen Huijuan Qiu Wancui Zhu Haohui Sun Jinsheng Huang Han Yang Wuguo Deng CPT1A promotes anoikis resistance in esophageal squamous cell carcinoma via redox homeostasis Redox Biology CPT1A Fatty acid oxidation Anoikis resistance Esophageal squamous cell carcinoma |
| title | CPT1A promotes anoikis resistance in esophageal squamous cell carcinoma via redox homeostasis |
| title_full | CPT1A promotes anoikis resistance in esophageal squamous cell carcinoma via redox homeostasis |
| title_fullStr | CPT1A promotes anoikis resistance in esophageal squamous cell carcinoma via redox homeostasis |
| title_full_unstemmed | CPT1A promotes anoikis resistance in esophageal squamous cell carcinoma via redox homeostasis |
| title_short | CPT1A promotes anoikis resistance in esophageal squamous cell carcinoma via redox homeostasis |
| title_sort | cpt1a promotes anoikis resistance in esophageal squamous cell carcinoma via redox homeostasis |
| topic | CPT1A Fatty acid oxidation Anoikis resistance Esophageal squamous cell carcinoma |
| url | http://www.sciencedirect.com/science/article/pii/S2213231722003160 |
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