The Underexplored Landscape of Hypoxia-Inducible Factor 2 Alpha and Potential Roles in Tumor Macrophages: A Review.
The Underexplored Landscape of Hypoxia-Inducible Factor 2 Alpha and Potential Roles in Tumor Macrophages: A Review.
复制标题
DOI：
10.3390/oxygen3010005
复制
发表时间：
2023-03
期刊：
影响因子：
--
通讯作者：
Eubank TD
中科院分区：
文献类型：
--
作者：
Steinberger KJ;Eubank TD
低组织氧合（称为缺氧）是实体瘤的一个特征，会带来负面后果。肿瘤相关巨噬细胞（TAM）在缺氧肿瘤区域积聚，并与多种肿瘤类型的癌症患者较差的预后相关。因此，在过去的十年中，巨噬细胞响应低氧张力的分子机制得到了越来越多的研究。缺氧可稳定一组缺氧诱导转录因子 (HIF)，据报道这些转录因子可驱动参与细胞存活、代谢和血管生成的转录程序。尽管肿瘤巨噬细胞 HIF-1α 和 HIF-2α 都与不利的肿瘤微环境相关，但大多数研究都集中在 HIF-1α 作为缺氧信号传导的主要调节因子，因为 HIF-1α 表达最初在多种癌症类型中被发现，并且与癌症患者较差的预后相关。人们对每个 HIFα 亚基对细胞表型的相对贡献知之甚少，尤其是在 TAM 中。曾经被认为具有重叠作用的巨噬细胞 HIF-2α 最近的研究证明了与 HIF-1α 不同的功能。在肿瘤生物学背景下，关于缺氧依赖性巨噬细胞 HIF-2α 与 HIF-1α 的差异作用的研究还很少。这篇综述强调了细胞 HIF-2α 的功能，并强调了肿瘤巨噬细胞 HIF-2α 氧依赖性功能研究中的空白。
Low tissue oxygenation, termed hypoxia, is a characteristic of solid tumors with negative consequences. Tumor-associated macrophages (TAMs) accumulate in hypoxic tumor regions and correlate with worse outcomes in cancer patients across several tumor types. Thus, the molecular mechanism in which macrophages respond to low oxygen tension has been increasingly investigated in the last decade. Hypoxia stabilizes a group of hypoxia-inducible transcription factors (HIFs) reported to drive transcriptional programs involved in cell survival, metabolism, and angiogenesis. Though both tumor macrophage HIF-1α and HIF-2α correlate with unfavorable tumor microenvironments, most research focuses on HIF-1α as the master regulator of hypoxia signaling, because HIF-1α expression was originally identified in several cancer types and correlates with worse outcome in cancer patients. The relative contribution of each HIFα subunit to cell phenotypes is poorly understood especially in TAMs. Once thought to have overlapping roles, recent investigation of macrophage HIF-2α has demonstrated a diverse function from HIF-1α. Little work has been published on the differential role of hypoxia-dependent macrophage HIF-2α when compared to HIF-1α in the context of tumor biology. This review highlights cellular HIF-2α functions and emphasizes the gap in research investigating oxygen-dependent functions of tumor macrophage HIF-2α.