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文章简介缺氧和细胞内钙瞬变是癌症的基本特征,而在缺氧肿瘤发生中,Ca~(2+)动员的方式和调控未知。在此项研究中,课题组发现,内质网钙感受器基质相互作用分子1(STIM1),与缺氧肝癌细胞高表达缺氧诱导因子-1α(HIF-1α)相关,且在肝癌生长期间上调。HIF-1可直接调控STIM1的转录和促进钙库操纵的Ca~(2+)内流(SOCE)。STIM1介导的SOCE通过激活钙/钙调蛋白依赖的蛋白激酶Ⅱ和P300对于HIF-1在缺氧肝癌中的表达非常重要。加入HIF-1抑制剂YC-1或敲降HIFIA,可显著减少缺氧上调的STIM1并抑制肿瘤发生。
INTRODUCTION Anoxia and intracellular calcium transients are the basic characteristics of cancer. However, the mechanism and regulation of Ca ~ (2+) mobilization in hypoxic tumorigenesis is unknown. In this study, the team found that the endoplasmic reticulum CaMV-STIM1 is associated with the high expression of hypoxia-inducible factor-1α (HIF-1α) in HCC cells and is up-regulated during HCC growth . HIF-1 directly regulates the transcription of STIM1 and promotes Ca 2+ manipulated Ca 2+ influx (SOCE). STIM1-mediated SOCE is important for HIF-1 expression in hypoxic liver cancer through activation of the calcium / calmodulin-dependent protein kinase II and P300. The addition of HIF-1 inhibitor YC-1 or knockdown of HIFIA significantly reduced hypoxia-upregulated STIM1 and inhibited tumorigenesis.