LYRM2 directly regulates complex I activity to support tumor growth in colorectal cancer by oxidative phosphorylation
LYRM2 directly regulates complex I activity to support tumor growth in colorectal cancer by oxidative phosphorylation
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DOI：
10.1016/j.canlet.2019.04.021
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发表时间：
2019-01-01
期刊：
影响因子：
9.7
通讯作者：
Huang, Jian
中科院分区：
文献类型：
--
作者：
Huang, Qi;Chen, Zhigang;Huang, Jian
氧化磷酸化（Oxidative phosphorylation，OXPHOS）在肿瘤中的作用引起了广泛关注，并在肿瘤的增殖、转移和耐药中发挥重要作用。然而，这些影响所涉及的机制至今仍不明确。在这项研究中，我们发现LYR motif containing 2（LYRM 2），一种新的分子，在结直肠癌中上调，并在体内和体外促进肿瘤生长。此外，我们发现LYRM 2位于线粒体中，直接与复合物I相互作用并增加其活性，从而促进大肠癌细胞中的OXPHOS。更重要的是，我们发现了一个新的Akt-S58 β-LYRM 2-复合物I轴，它负责LYRM 2诱导的肿瘤生长和OXPHOS在结直肠癌中的激活。我们的发现阐明了LYRM 2在调节肿瘤代谢中的作用，并为结直肠癌治疗提供了一个新的潜在靶点。
Oxidative phosphorylation (OXPHOS) in cancer has attracted a considerable attention in the past decades, and accumulated evidence has suggested that it plays an important role in tumor proliferation, metastasis and drug resistance. However, the mechanisms involved in these effects are still ambiguous to date. In this study, we found that LYR motif containing 2 (LYRM2), a novel molecule, is up-regulated in colorectal cancer and promotes tumor growth both in vivo and in vitro. Furthermore, we discovered that LYRM2 locates in the mitochondria, directly interacts with complex I and increases its activity, thus promoting OXPHOS in colorectal cancer cells. More importantly, we identified a new Akt-S58phos-LYRM2-Complex I axis, which is responsible for the LYRM2-induced tumor growth and the activation of OXPHOS in colorectal cancer. Our finding illustrates the role of LYRM2 in regulating tumor metabolism and provides a new potential target for colorectal cancer treatment.