CPT1C-mediated fatty acid oxidation facilitates colorectal cancer cell proliferation and metastasis
Fatty acid oxidation (FAO) has been proven to be an accomplice in tumor progression. Carnitine palmitoyltransferase 1C (CPT1C), a rate-limiting enzyme in FAO, mainly functions to catalyze fatty acid carnitinylation and guarantee subsequent entry into the mitochondria for FAO in colorectal cancer (CR...
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2023-04-01
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| Series: | Acta Biochimica et Biophysica Sinica |
| Subjects: | |
| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2023041 |
| _version_ | 1797635898882392064 |
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| author | Li Jing Zheng Wanwei Wu Jie Zhang Jun Lv Bin Li Wenshuai Liu Jie Zhang Xin Huang Tiansheng Luo Zhongguang |
| author_facet | Li Jing Zheng Wanwei Wu Jie Zhang Jun Lv Bin Li Wenshuai Liu Jie Zhang Xin Huang Tiansheng Luo Zhongguang |
| author_sort | Li Jing |
| collection | DOAJ |
| description | Fatty acid oxidation (FAO) has been proven to be an accomplice in tumor progression. Carnitine palmitoyltransferase 1C (CPT1C), a rate-limiting enzyme in FAO, mainly functions to catalyze fatty acid carnitinylation and guarantee subsequent entry into the mitochondria for FAO in colorectal cancer (CRC). Gene expression data and clinical information extracted from The Cancer Genome Atlas (TCGA) database show significantly higher expression of CPT1C in patients with metastatic CRC ( P=0.005). Moreover, overexpression of CPT1C is correlated with worse relapse-free survival in CRC (HR 2.1, P=0.0006), while no statistical significance is indicated for CPT1A and CPT1B. Further experiments demonstrate that downregulation of CPT1C expression leads to a decrease in the FAO rate, suppression of cell proliferation, cell cycle arrest and repression of cell migration in CRC, whereas opposite results are obtained when CPT1C is overexpressed. Furthermore, an FAO inhibitor almost completely reverses the enhanced cell proliferation and migration induced by CPT1C overexpression. In addition, analysis of TCGA data illustrates a positive association between CPT1C expression and HIF1α level, suggesting that CPT1C is a transcriptional target of HIF1α. In conclusion, CPT1C overexpression indicates poor relapse-free survival of patients with CRC, and CPT1C is transcriptionally activated by HIF1α, thereby promoting the proliferation and migration of CRC cells. |
| first_indexed | 2024-03-11T12:26:41Z |
| format | Article |
| id | doaj.art-62aacb93d35d4bf4935e06051f287ab5 |
| institution | Directory Open Access Journal |
| issn | 1672-9145 |
| language | English |
| last_indexed | 2024-03-11T12:26:41Z |
| publishDate | 2023-04-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj.art-62aacb93d35d4bf4935e06051f287ab52023-11-06T08:34:54ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452023-04-01551301130910.3724/abbs.202304120d259ccCPT1C-mediated fatty acid oxidation facilitates colorectal cancer cell proliferation and metastasisLi Jing0Zheng Wanwei1Wu Jie2Zhang Jun3Lv Bin4Li Wenshuai5Liu Jie6Zhang Xin7Huang Tiansheng8Luo Zhongguang9["Department of CyberKnife Center, Huashan Hospital, Fudan University, Shanghai 200040, China"]["Department of Digestive Diseases of Huashan Hospital, Fudan University, Shanghai 200040, China"]["Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou 215000, China"]["Department of Digestive Diseases of Huashan Hospital, Fudan University, Shanghai 200040, China"]["Department of Digestive Diseases of Huashan Hospital, Fudan University, Shanghai 200040, China"]["Department of Digestive Diseases of Huashan Hospital, Fudan University, Shanghai 200040, China"]["Department of Digestive Diseases of Huashan Hospital, Fudan University, Shanghai 200040, China"]["Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai 200025, China"]["Department of Digestive Diseases, Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200052, China"]["Department of Digestive Diseases of Huashan Hospital, Fudan University, Shanghai 200040, China"]Fatty acid oxidation (FAO) has been proven to be an accomplice in tumor progression. Carnitine palmitoyltransferase 1C (CPT1C), a rate-limiting enzyme in FAO, mainly functions to catalyze fatty acid carnitinylation and guarantee subsequent entry into the mitochondria for FAO in colorectal cancer (CRC). Gene expression data and clinical information extracted from The Cancer Genome Atlas (TCGA) database show significantly higher expression of CPT1C in patients with metastatic CRC ( P=0.005). Moreover, overexpression of CPT1C is correlated with worse relapse-free survival in CRC (HR 2.1, P=0.0006), while no statistical significance is indicated for CPT1A and CPT1B. Further experiments demonstrate that downregulation of CPT1C expression leads to a decrease in the FAO rate, suppression of cell proliferation, cell cycle arrest and repression of cell migration in CRC, whereas opposite results are obtained when CPT1C is overexpressed. Furthermore, an FAO inhibitor almost completely reverses the enhanced cell proliferation and migration induced by CPT1C overexpression. In addition, analysis of TCGA data illustrates a positive association between CPT1C expression and HIF1α level, suggesting that CPT1C is a transcriptional target of HIF1α. In conclusion, CPT1C overexpression indicates poor relapse-free survival of patients with CRC, and CPT1C is transcriptionally activated by HIF1α, thereby promoting the proliferation and migration of CRC cells. https://www.sciengine.com/doi/10.3724/abbs.2023041colorectal cancerfatty acid oxidationCPT1Ccell proliferationcell migration |
| spellingShingle | Li Jing Zheng Wanwei Wu Jie Zhang Jun Lv Bin Li Wenshuai Liu Jie Zhang Xin Huang Tiansheng Luo Zhongguang CPT1C-mediated fatty acid oxidation facilitates colorectal cancer cell proliferation and metastasis Acta Biochimica et Biophysica Sinica colorectal cancer fatty acid oxidation CPT1C cell proliferation cell migration |
| title | CPT1C-mediated fatty acid oxidation facilitates colorectal cancer cell proliferation and metastasis |
| title_full | CPT1C-mediated fatty acid oxidation facilitates colorectal cancer cell proliferation and metastasis |
| title_fullStr | CPT1C-mediated fatty acid oxidation facilitates colorectal cancer cell proliferation and metastasis |
| title_full_unstemmed | CPT1C-mediated fatty acid oxidation facilitates colorectal cancer cell proliferation and metastasis |
| title_short | CPT1C-mediated fatty acid oxidation facilitates colorectal cancer cell proliferation and metastasis |
| title_sort | cpt1c mediated fatty acid oxidation facilitates colorectal cancer cell proliferation and metastasis |
| topic | colorectal cancer fatty acid oxidation CPT1C cell proliferation cell migration |
| url | https://www.sciengine.com/doi/10.3724/abbs.2023041 |
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