Laboratory of Metabolic Dynamics in Cancer, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo TO, Italy.
Laboratory of Metabolic Dynamics in Cancer, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo TO, Italy.
Semin Cell Dev Biol. 2020 Feb;98:63-70. doi: 10.1016/j.semcdb.2019.05.018. Epub 2019 May 28.
Colorectal cancer (CRC) is one of the most common types of cancer worldwide. Despite recent advances in the molecular genetics of CRC, poor treatment outcomes highlight the need for a better understanding of the underlying mechanisms accounting for tumor initiation and progression. Recently, deregulation of cellular metabolism has emerged as a key hallmark of cancer. Reprogramming of core cellular metabolic pathways by cancer cells provides energy, anaplerotic precursors and reducing equivalents required to support tumor growth. Here, we review key findings implicating cancer metabolism as a major contributor of tumor initiation, growth and metastatic dissemination in CRC. We summarize the metabolic pathways governing stem cell fate in the intestine, the metabolic adaptations of proliferating colon cancer cells and their crosstalk with oncogenic signaling, and how they fulfill the energetic demands imposed by the metastatic cascade. Lastly, we discuss how some of these metabolic pathways could represent new vulnerabilities of CRC cells with the potential to be targeted.
结直肠癌(CRC)是全球最常见的癌症类型之一。尽管 CRC 分子遗传学最近取得了进展,但治疗效果不佳突出表明需要更好地了解导致肿瘤发生和进展的潜在机制。最近,细胞代谢失调已成为癌症的一个关键标志。癌细胞对核心细胞代谢途径的重编程为肿瘤生长提供了所需的能量、氨酰基前体和还原当量。在这里,我们回顾了将癌症代谢作为 CRC 中肿瘤起始、生长和转移扩散的主要贡献者的关键发现。我们总结了调节肠道干细胞命运的代谢途径、增殖结肠癌细胞的代谢适应及其与致癌信号的相互作用,以及它们如何满足转移级联产生的能量需求。最后,我们讨论了这些代谢途径中的一些如何成为 CRC 细胞的新弱点,并有可能成为治疗靶点。