生物
血管生成
PI3K/AKT/mTOR通路
癌症研究
癌症
转录因子
蛋白激酶B
转移
平方毫米
信号转导
癌细胞
缺氧诱导因子
肿瘤进展
细胞生物学
HIF1A型
基因
遗传学
作者
Mohsen Rashid,Leila Rostami Zadeh,Behzad Baradaran,Ommoleila Molavi,Zeinab Ghesmati,Mehdi Sabzichi,Fatemeh Ramezani
出处
期刊:Gene
[Elsevier]
日期:2021-06-25
卷期号:798: 145796-145796
被引量:142
标识
DOI:10.1016/j.gene.2021.145796
摘要
Hypoxia induicible factor-1 alpha (HIF-1α) is a key transcription factor in cancer progression and target therapy in cancer. HIF-1α acts differently depending on presence or absence of Oxygen. In an oxygen-immersed environment, HIF-1α completely deactivated and destroyed by the ubiquitin proteasome pathway (UPP). In contrast, in the oxygen-free environment, it escapes destruction and enters to the nucleus of cells then upregulates many genes involved in cancer progression. Overexpressed HIF-1α and downstream genes support cancer progression through various mechanisms including angiogenesis, proliferation and survival of cells, metabolism reprogramming, invasion and metastasis, cancer stem cell maintenance, induction of genetic instability, and treatment resistance. HIF-1α can be provoked by signaling pathways unrelated to hypoxia during cancer progression. Therefore, cancer development and progression can be modulated by targeting HIF-1α and its downstream signaling molecules. In this regard, HIF-1α inhibitors which are categorized into the agents that regulate HIF-1α in gene, mRNA and protein levels used as an efficient way in cancer treatment. Also, HIF-1α expression can be negatively affected by the agents suppressing the activation of mTOR, PI3k/Akt and MAPK pathways.
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