| Literature DB >> 29995871 |
Ying-Nan Wang1, Zhao-Lei Zeng1, Jiahuan Lu1, Yun Wang1, Ze-Xian Liu1, Ming-Ming He1, Qi Zhao1, Zi-Xian Wang1, Ting Li1, Yun-Xin Lu1, Qi-Nian Wu1, Kai Yu1, Feng Wang1, Heng-Ying Pu1, Bo Li2, Wei-Hua Jia1, Ming Shi1, Dan Xie1, Tie-Bang Kang1, Peng Huang3, Huai-Qiang Ju4, Rui-Hua Xu5.
Abstract
Anoikis is a critical obstacle to cancer metastasis. Colorectal cancer (CRC) exhibits a high rate of metastasis, leading to death, and the mechanisms involved in anoikis resistance are still unclear. We identified that the fatty acid oxidation (FAO) pathway was activated in detached CRC cells. Multiple genes in the FAO pathway, specifically the rate-limiting enzyme CPT1A, were upregulated in CRC cells grown in suspension. Reactive oxygen species elimination mediated by CPT1A in CRC cells was vital to anoikis resistance. In vivo experiments showed that CPT1A-suppressed CRC cells colonized the lung at a much lower rate than normal CRC cells, suggesting that CPT1A-mediated FAO activation increased metastatic capacity. In clinical tissue specimens from CRC patients, elevated expression of CPT1A was observed in metastatic sites compared with primary sites. Our results demonstrate that CPT1A-mediated FAO activation induces CRC cells to resist anoikis, suggesting that CPT1A is an attractive target for treating metastatic CRC.Entities:
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Year: 2018 PMID： 29995871 DOI： 10.1038/s41388-018-0384-z
Source DB: PubMed Journal: Oncogene ISSN： 0950-9232 Impact factor: 9.867