Wang Gang, Wang Jun-Jie, Yin Pei-Hao, Xu Ke, Wang Yu-Zhu, Shi Feng, Gao Jing, Fu Xing-Li
Department of Pharmaceutics, Shanghai Eighth People's Hospital, Jiangsu University, Shanghai, China.
Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
J Cell Biochem. 2019 Feb;120(2):1106-1121. doi: 10.1002/jcb.27558. Epub 2018 Oct 26.
Alterations in cellular energy metabolism play critical roles in colorectal cancer (CRC). These alterations, which correlate to KRAS mutations, have been identified as energy metabolism signatures. This review summarizes the relationship between colorectal tumors associated with mutated KRAS and energy metabolism, especially for the deregulated energy metabolism that affects tumor cell proliferation, invasion, and migration. Furthermore, this review will concentrate on the role of metabolic genes, factors and signaling pathways, which are coupled with the primary energy source connected with the KRAS mutation that induces metabolic alterations. Strategies for targeting energy metabolism in mutated KRAS CRC are also introduced. In conclusion, deregulated energy metabolism has a close relationship with KRAS mutations in colorectal tumors. Therefore, selective inhibitors, agents against metabolic targets or KRAS signaling, may be clinically useful for colorectal tumor treatment through a patient-personalized approach.
细胞能量代谢的改变在结直肠癌(CRC)中起着关键作用。这些与KRAS突变相关的改变已被确定为能量代谢特征。本综述总结了与KRAS突变相关的结直肠肿瘤与能量代谢之间的关系,特别是对于影响肿瘤细胞增殖、侵袭和迁移的失调能量代谢。此外,本综述将集中探讨代谢基因、因子和信号通路的作用,这些与诱导代谢改变的KRAS突变相关的主要能量来源相关联。还介绍了针对KRAS突变型CRC中能量代谢的策略。总之,失调的能量代谢与结直肠肿瘤中的KRAS突变密切相关。因此,选择性抑制剂、针对代谢靶点或KRAS信号的药物,可能通过患者个性化方法在结直肠肿瘤治疗中具有临床应用价值。