Department of Surgical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China; Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou, 310009, China; Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
Department of Surgical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China; Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou, 310009, China.
Cancer Lett. 2019 Jul 28;455:36-47. doi: 10.1016/j.canlet.2019.04.021. Epub 2019 Apr 17.
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.
在过去的几十年中，癌症中的氧化磷酸化（OXPHOS）引起了相当大的关注，并且已有大量证据表明，它在肿瘤增殖、转移和耐药性中发挥重要作用。然而，迄今为止，这些作用涉及的机制仍不明确。在这项研究中，我们发现含有 LYR 基序的 2 型（LYRM2）是一种新型分子，在结直肠癌中上调，并促进体内和体外的肿瘤生长。此外，我们发现 LYRM2 位于线粒体中，直接与复合物 I 相互作用并增加其活性，从而促进结直肠癌细胞中的 OXPHOS。更重要的是，我们确定了一个新的 Akt-S58phos-LYRM2-Complex I 轴，该轴负责 LYRM2 诱导的肿瘤生长和结直肠癌细胞中 OXPHOS 的激活。我们的发现说明了 LYRM2 在调节肿瘤代谢中的作用，并为结直肠癌的治疗提供了一个新的潜在靶点。
