College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250022, China.
College of Traditional Chinese Medicine, Weifang Medical University, Weifang 261000, China.
Biomed Pharmacother. 2022 Dec;156:113861. doi: 10.1016/j.biopha.2022.113861. Epub 2022 Oct 10.
Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is highly aggressive and hypoxic compared with other subtypes. The role of hypoxia inducible factor 1α (HIF-1α) as a key hypoxic transcription factor in oncogenic processes has been extensively studied. Recently, it has been shown that HIF-1α regulates the complex biological processes of TNBC, such as glycolysis, angiogenesis, invasion and metastasis, breast cancer stem cells (BCSCs) enrichment, and immune escape, to promote TNBC survival and development through the activation of downstream target genes. In addition, inflammatory mediators, oxygen levels, noncoding RNAs, complex signaling regulatory networks, epigenetic regulators are involved in the upstream regulatory expression of HIF-1α. However, further studies are needed to determine the potential and future directions of targeting HIF-1α in TNBC. This article discusses the expression of the HIF-1α transcription factor in TNBC. We also explored the mechanism by which HIF-1α drives TNBC progression. The potential significance of targeting HIF-1α for immunotherapy, chemotherapy, anti-angiogenic therapy, and photodynamic therapy is discussed. The intrinsic mechanism, existing problems and future directions of targeting HIF-1α are also studied.
三阴性乳腺癌（TNBC）是一种侵袭性较强的乳腺癌亚型，与其他亚型相比，其缺氧程度更高。缺氧诱导因子 1α（HIF-1α）作为癌基因过程中的关键缺氧转录因子的作用已得到广泛研究。最近，研究表明 HIF-1α 通过激活下游靶基因，调节 TNBC 的复杂生物学过程，如糖酵解、血管生成、侵袭和转移、乳腺癌干细胞（BCSCs）富集和免疫逃逸，促进 TNBC 的存活和发展。此外，炎症介质、氧水平、非编码 RNA、复杂信号转导调控网络、表观遗传调控因子参与 HIF-1α 的上游调控表达。然而，仍需要进一步研究以确定靶向 HIF-1α 在 TNBC 中的潜在和未来方向。本文讨论了 HIF-1α 转录因子在 TNBC 中的表达。我们还探讨了 HIF-1α 驱动 TNBC 进展的机制。讨论了靶向 HIF-1α 用于免疫治疗、化疗、抗血管生成治疗和光动力治疗的潜在意义。还研究了靶向 HIF-1α 的内在机制、存在的问题和未来方向。
