Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan, China.
Department of Cardiovascular Surgery, The Second Xiangya Hospital of CentralSouth University, Changsha, Hunan, China.
Exp Cell Res. 2020 Oct 1;395(1):112175. doi: 10.1016/j.yexcr.2020.112175. Epub 2020 Jul 15.
Autophagy is a basic catabolic response that eukaryotic cells use to degrade unnecessary or dysfunctional cellular components in an orderly and regulated manner. It plays important roles in maintaining cellular homeostasis, energy homeostasis, response to environmental stimuli, and the development of cancer. In solid tumors, hypoxia induces an increased HIF-1a that activates autophagy. However, the exact mechanism by which induced HIF-1a stimulates autophagy in cancer cells remains elusive. In the present study, we confirmed that ANKRD37 is upregulated in colon cancer tissue. Moreover, the higher expression level of ANKRD37 is related to a poorer survival rate. Using RNA interference, immunoblot, and immunofluorescence, we discovered that in cancer cell line RKO, hypoxia-induced HIF-1a regulates autophagy activity by increasing ANKRD37 level. In addition, intranuclear ANKRD37 played an important role in the regulation of hypoxia-induced autophagy. The translocation of ANKRD37 into cell nuclear is required for promoting cell growth and HIF-1a induced autophagy. These findings provide new insights to understand the hypoxia regulation mechanisms and the role of autophagy in cancer development.
自噬是真核细胞用来以有序和受调控的方式降解不必要或功能失调的细胞成分的基本分解代谢反应。它在维持细胞内环境稳定、能量内环境稳定、对环境刺激的反应以及癌症发展中发挥重要作用。在实体瘤中，缺氧诱导 HIF-1a 增加，从而激活自噬。然而，诱导的 HIF-1a 刺激癌细胞自噬的确切机制仍不清楚。在本研究中，我们证实 ANKRD37 在结肠癌组织中上调。此外，ANKRD37 的高表达水平与较差的生存率相关。通过 RNA 干扰、免疫印迹和免疫荧光，我们发现，在结肠癌细胞系 RKO 中，缺氧诱导的 HIF-1a 通过增加 ANKRD37 水平来调节自噬活性。此外，核内 ANKRD37 在调节缺氧诱导的自噬中发挥重要作用。ANKRD37 向细胞核内的易位对于促进细胞生长和 HIF-1a 诱导的自噬是必需的。这些发现为理解缺氧调节机制以及自噬在癌症发展中的作用提供了新的见解。
