The hypoxic condition has a pivotal role in solid tumors and was shown to correlate with the poor outcome of anticancer treatments. Hypoxia contributes to tumor progression and leads to therapy resistance. Two forms of a hypoxic environment might have relevance in tumor mass formation: chronic and cyclic hypoxia. The main regulators of hypoxia are hypoxia-inducible factors, which regulate the cell survival, proliferation, motility, metabolism, pH, extracellular matrix function, inflammatory cells recruitment and angiogenesis. The metastatic process consists of different steps in which hypoxia-inducible factors can play an important role. Rac1, belonging to small G-proteins, is involved in the metastasis process as one of the key molecules of migration, especially in a hypoxic environment. The effect of hypoxia on the tumor phenotype and the signaling pathways which may interfere with tumor progression are already quite well known. Although the role of Rac1, one of the small G-proteins, in hypoxia remains unclear, predominantly, in vitro studies performed so far confirm that Rac1 inhibition may represent a viable direction for tumor therapy.
缺氧状态在实体肿瘤中具有关键作用，并被证实与抗癌治疗效果不佳相关。缺氧不仅促进肿瘤进展，还会导致治疗抵抗。肿瘤团块形成过程中可能存在两种相关的缺氧环境类型：慢性缺氧与周期性缺氧。缺氧的主要调控因子是缺氧诱导因子，其可调节细胞存活、增殖、运动、代谢、pH值、细胞外基质功能、炎症细胞募集及血管生成。在转移过程的多个环节中，缺氧诱导因子均可能发挥重要作用。Rac1作为小G蛋白家族成员，是细胞迁移的关键分子之一，尤其在缺氧环境中参与转移过程。目前关于缺氧对肿瘤表型的影响及其干扰肿瘤进展的信号通路已有较充分认识。尽管小G蛋白家族成员Rac1在缺氧环境中的作用机制尚未完全阐明，但现有体外研究普遍证实，抑制Rac1活性可能成为肿瘤治疗的可行方向。
Role of Hypoxia and Rac1 Inhibition in the Metastatic Cascade
肿瘤(癌症)患者之家