失巢
生物
结直肠癌
癌症研究
转移
下调和上调
癌症
内科学
生物化学
医学
基因
遗传学
作者
Ying Nan Wang,Zhao Lei Zeng,Jiahuan Lu,Yun Wang,Zexian Liu,Ming He,Qi Zhao,Zi‐Xian Wang,Ting Li,Yun Lü,Qi Wu,Kai Yu,Feng Wang,Heng Ying Pu,Bo Li,Wei Jia,Ming Shi,Dan Xie,Tie Bang Kang,Peng Huang,Huai‐Qiang Ju,Rui‐Hua Xu
出处
期刊:Oncogene
[Springer Nature]
日期:2018-07-11
卷期号:37 (46): 6025-6040
被引量:216
标识
DOI:10.1038/s41388-018-0384-z
摘要
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.
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