The Interplay Between Tumor Suppressor p53 and Hypoxia Signaling Pathways in Cancer.
The Interplay Between Tumor Suppressor p53 and Hypoxia Signaling Pathways in Cancer.
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DOI：
10.3389/fcell.2021.648808
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发表时间：
2021
影响因子：
5.5
通讯作者：
Feng Z
中科院分区：
文献类型：
--
作者：
Zhang C;Liu J;Wang J;Zhang T;Xu D;Hu W;Feng Z
低氧是实体瘤的一个标志，在肿瘤进展的不同阶段起着关键作用，包括肿瘤细胞的增殖、存活、血管生成、转移、代谢重编程和干细胞分化。低氧诱导因子(HIF)信号的激活在调节肿瘤的低氧反应中起着关键作用。P53作为一种关键的肿瘤抑制因子和转录因子，响应包括缺氧在内的多种应激信号，选择性地转录其靶基因，调节各种细胞反应，发挥其在肿瘤抑制中的作用。研究表明，缺氧和P53信号通路之间存在密切而复杂的相互作用。根据细胞/组织类型以及缺氧的严重程度和持续时间的不同，P53的水平和活性可以受到不同的缺氧和HIF信号的调节。另一方面，P53在多个水平上调控缺氧和HIF信号传导。许多肿瘤相关突变型P53蛋白显示出功能获得(GOF)致癌活性，以促进癌症进展。新的证据也表明，GOF突变体P53可以通过与缺氧和HIF信号通路的相互作用而促进癌症的进展。在这篇综述中，我们总结了我们目前对缺氧和P53信号通路之间相互作用的理解，它对癌症进展的影响，以及它在癌症治疗中的潜在应用。
Hypoxia is a hallmark of solid tumors and plays a critical role in different steps of tumor progression, including proliferation, survival, angiogenesis, metastasis, metabolic reprogramming, and stemness of cancer cells. Activation of the hypoxia-inducible factor (HIF) signaling plays a critical role in regulating hypoxic responses in tumors. As a key tumor suppressor and transcription factor, p53 responds to a wide variety of stress signals, including hypoxia, and selectively transcribes its target genes to regulate various cellular responses to exert its function in tumor suppression. Studies have demonstrated a close but complex interplay between hypoxia and p53 signaling pathways. The p53 levels and activities can be regulated by the hypoxia and HIF signaling differently depending on the cell/tissue type and the severity and duration of hypoxia. On the other hand, p53 regulates the hypoxia and HIF signaling at multiple levels. Many tumor-associated mutant p53 proteins display gain-of-function (GOF) oncogenic activities to promote cancer progression. Emerging evidence has also shown that GOF mutant p53 can promote cancer progression through its interplay with the hypoxia and HIF signaling pathway. In this review, we summarize our current understanding of the interplay between the hypoxia and p53 signaling pathways, its impact upon cancer progression, and its potential application in cancer therapy.
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DOI：
10.1073/pnas.1808314115
发表时间：
2018-11-13
影响因子：
11.1
作者：
Amelio I;Mancini M;Petrova V;Cairns RA;Vikhreva P;Nicolai S;Marini A;Antonov AA;Le Quesne J;Baena Acevedo JD;Dudek K;Sozzi G;Pastorino U;Knight RA;Mak TW;Melino G
通讯作者：
Melino G
影响因子：
3.3
作者：
Bratasz, Anna;Pandian, Ramasamy P.;Kuppusamy, Periannan
通讯作者：
Kuppusamy, Periannan
影响因子：
82.9
作者：
Choueiri, Toni K.;Kaelin, William G., Jr.
通讯作者：
Kaelin, William G., Jr.
影响因子：
9.8
作者：
Dangelmaier, Emily;Lazar, Sarah B.;Lal, Ashish
通讯作者：
Lal, Ashish
影响因子：
5.5
作者：
Chen, Baosheng;Longtine, Mark S.;Nelson, D. Michael
通讯作者：
Nelson, D. Michael