Jiang Siyuan, Han Xiaoqi, Zhao Zidong, Song Dalong, Cheng Shuwen, Liu Tihui, Zhao Xujie, Gu Yinmin, Duan Liqiang, Gao Shan
Zhongda Hospital, Medical School, Advanced Institute for Life and Health, Southeast University, Nanjing, 210096, China.
Shanxi Academy of Advanced Research and Innovation, Taiyuan, 030032, China; Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Southeast University, Nanjing, 210096, China.
Biochem Biophys Res Commun. 2023 Nov 12;681:271-275. doi: 10.1016/j.bbrc.2023.09.074. Epub 2023 Sep 27.
Hypoxia is a common hallmark of cancer and plays a crucial role in promoting epithelial-mesenchymal transition (EMT). Hormonally Upregulated Neu-associated Kinase (HUNK) regulates EMT through its kinase activity. However, whether hypoxia is involved in HUNK-mediated EMT is incompletely understood. This study unveils an association between HUNK kinase activity and hypoxia in colorectal cancer (CRC). Importantly, hypoxia does not alter the expression levels of HUNK, but directly affects the phosphorylation levels of downstream proteins with indication of HUNK activity. Functionally, the upregulation of migration, invasion, and expression of EMT markers in CRC cells under hypoxic conditions can be attributed, in part, to the downregulation of HUNK-mediated phosphorylation of downstream proteins. These findings highlight the intricate relationship between HUNK, hypoxia and the molecular mechanisms of cancer EMT. Understanding these mechanisms may provide valuable insights into therapeutic targets for inhibiting cancer metastasis.
缺氧是癌症的一个常见特征，在促进上皮-间质转化（EMT）中起关键作用。激素上调的神经相关激酶（HUNK）通过其激酶活性调节EMT。然而，缺氧是否参与HUNK介导的EMT尚未完全明确。本研究揭示了结直肠癌（CRC）中HUNK激酶活性与缺氧之间的关联。重要的是，缺氧不会改变HUNK的表达水平，但会直接影响下游蛋白的磷酸化水平，提示HUNK活性。在功能上，缺氧条件下CRC细胞迁移、侵袭和EMT标志物表达的上调，部分可归因于HUNK介导的下游蛋白磷酸化的下调。这些发现突出了HUNK、缺氧与癌症EMT分子机制之间的复杂关系。了解这些机制可能为抑制癌症转移的治疗靶点提供有价值的见解。
