The HIF-1 alpha as a Potent Inducer of the Hallmarks in Gastric Cancer

Hypoxia is the principal architect of the topographic heterogeneity in tumors. Hypoxiainducible factor-1 alpha (HIF-1 alpha) reinforces all hallmarks of cancer and donates cancer cells with more aggressive characteristics at hypoxic niches. HIF-1 alpha 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-1 alpha is also associated with genetic instability, tumor-promoting inflammation, and escape from immunity. Therefore, HIF-1 alpha may be an important therapeutic target in cancer. Despite that, the drug market lacks safe and efficacious anti-HIF-1 alpha molecules, raising the quest for fully unveiling the complex interactome of HIF-1 alpha 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-1 alpha 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-1 alpha on the cancer hallmarks with a specific focus on gastric cancer.

Automated summary

Hypoxia plays a crucial role in the heterogeneity of tumors, and HIF-1 alpha reinforces cancer hallmarks and enhances the aggressiveness of cancer cells in hypoxic niches. However, the understanding of the role of HIF-1 alpha in gastric cancer is limited, highlighting the need for further research.