西亚试剂：STIM1 Mediates Hypoxia-Driven Hepatocarcinogenesis via Inte

Hypoxia and intracellular Ca2+ transients are fundamental traits of cancer, wheras the route and regulation of Ca2+ mobilization in hypoxic tumorigenesis are unknown. Here, we show that stromal-interaction molecule 1 (STIM1), an ER Ca2+ sensor, correlates with elevated hypoxia-inducible factor-1 alpha (HIF-1α) in hypoxic hepatocarcinoma cells (HCCs) and is upregulated during hepatocarcinoma growth. HIF-1 directly controls STIM1 transcription and contributes to store-operated Ca2+ entry (SOCE). STIM1-mediated SOCE is also required for HIF-1 accumulation in hypoxic HCCs via activation of Ca2+/calmodulin-dependent protein kinase II and p300. Administration of YC-1, a HIF-1 inhibitor, or knockdown of HIF1A significantly diminishes hypoxia-enhanced STIM1 and suppresses tumorigenesis. Moreover, ectopic expression of STIM1 or HIF-1α partially reverses impaired growth of tumors treated with YC-1. These results suggest a mutual dependency and regulation of STIM1 and HIF-1 in controlling Ca2+ mobilization and hypoxic tumor growth and highlight a potential target for early hypoxia-related intervention.以上资料由西亚试剂：http://www.xiyashiji.com/ 提供