Ucaryilmaz Metin Cemre, Ozcan Gulnihal
Graduate School of Health Sciences, Koç University, 34450 Istanbul, Turkey.
Department of Medical Pharmacology, School of Medicine, Koç University, 34450 Istanbul, Turkey.
Cancers (Basel). 2022 May 30;14(11):2711. doi: 10.3390/cancers14112711.
Hypoxia is the principal architect of the topographic heterogeneity in tumors. Hypoxia-inducible factor-1α (HIF-1α) reinforces all hallmarks of cancer and donates cancer cells with more aggressive characteristics at hypoxic niches. HIF-1α potently induces sustained growth factor signaling, angiogenesis, epithelial-mesenchymal transition, and replicative immortality. Hypoxia leads to the selection of cancer cells that evade growth suppressors or apoptotic triggers and deregulates cellular energetics. HIF-1α is also associated with genetic instability, tumor-promoting inflammation, and escape from immunity. Therefore, HIF-1α may be an important therapeutic target in cancer. Despite that, the drug market lacks safe and efficacious anti-HIF-1α molecules, raising the quest for fully unveiling the complex interactome of HIF-1α in cancer to discover more effective strategies. The knowledge gap is even wider in gastric cancer, where the number of studies on hypoxia is relatively low compared to other well-dissected cancers. A comprehensive review of the molecular mechanisms by which HIF-1α induces gastric cancer hallmarks could provide a broad perspective to the investigators and reveal missing links to explore in future studies. Thus, here we review the impact of HIF-1α on the cancer hallmarks with a specific focus on gastric cancer.
缺氧是肿瘤地形异质性的主要成因。缺氧诱导因子-1α（HIF-1α）强化了癌症的所有特征，并使癌细胞在缺氧微环境中具有更强的侵袭性。HIF-1α有力地诱导持续的生长因子信号传导、血管生成、上皮-间质转化和复制永生。缺氧导致选择逃避生长抑制因子或凋亡触发因子的癌细胞，并使细胞能量代谢失调。HIF-1α还与基因不稳定、肿瘤促进性炎症和免疫逃逸有关。因此，HIF-1α可能是癌症的一个重要治疗靶点。尽管如此，药物市场缺乏安全有效的抗HIF-1α分子，这就需要全面揭示HIF-1α在癌症中的复杂相互作用组，以发现更有效的策略。在胃癌方面，知识差距甚至更大，与其他已深入研究的癌症相比，关于缺氧的研究数量相对较少。全面综述HIF-1α诱导胃癌特征的分子机制，可为研究人员提供广阔的视角，并揭示未来研究中有待探索的缺失环节。因此，在此我们综述HIF-1α对癌症特征的影响，特别关注胃癌。
