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.

中文翻译：

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CPT1A介导的脂肪酸氧化可通过抑制缺氧促进大肠癌细胞的转移。

失语症是癌症转移的关键障碍。大肠癌（CRC）表现出高转移率，导致死亡，而对厌食症的抵抗机制尚不清楚。我们确定，脂肪酸氧化（FAO）通路被激活在分离的CRC细胞中。FAO途径中的多个基因，特别是限速酶CPT1A，在悬浮培养的CRC细胞中被上调。CPT1A介导的CRC细胞中活性氧的消除对于阳极抗性至关重要。体内实验表明，受CPT1A抑制的CRC细胞在肺部定植的速率比正常CRC细胞低得多，这表明CPT1A介导的FAO激活可提高转移能力。在CRC患者的临床组织标本中，与主要部位相比，在转移部位观察到CPT1A表达升高。我们的研究结果表明，CPT1A介导的FAO激活诱导CRC细胞抵抗无神经，这表明CPT1A是治疗转移性CRC的诱人靶标。