HIF-1 and NRF2; Key Molecules for Malignant Phenotypes of Pancreatic Cancer.
HIF-1 and NRF2; Key Molecules for Malignant Phenotypes of Pancreatic Cancer.
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DOI：
10.3390/cancers14020411
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发表时间：
2022-01-14
期刊：
影响因子：
5.2
通讯作者：
Masamune A
中科院分区：
文献类型：
--
作者：
Hamada S;Matsumoto R;Masamune A
胰腺癌进展涉及癌细胞和基质细胞在恶劣的肿瘤微环境中的相互作用，其特征在于缺氧，营养物质少和氧化应激。在临床上，癌细胞克服治疗干预，如化疗和放疗，继续生存。适应机制的激活是癌细胞在这些条件下存活所必需的，并且它也有助于恶性表型的获得。基质细胞，特别是胰腺星状细胞，在形成促癌微环境中起关键作用。本文综述了缺氧诱导因子-1和KEAP 1-NRF 2在胰腺癌细胞和星状细胞适应缺氧和氧化应激的应激反应机制中的作用。与这些分子相关的各种癌症促进特性已经被确定，并且它们可能在未来作为新的治疗靶点。胰腺癌由于早期进展和对常规治疗的抵抗而难以治疗。致密的纤维化间质，称为结缔组织增生，是胰腺癌的特征性特征，并通过胰腺癌细胞和间质细胞（包括胰腺星状细胞）之间的相互作用而发展。致密的间质形成了以缺氧、营养物质少和氧化应激为特征的恶劣的肿瘤微环境。胰腺癌细胞以及胰腺星状细胞通过改变由各种应激反应机制控制的信号分子、转运蛋白和代谢酶的表达而在恶劣的微环境中存活。缺氧诱导因子-1和KEAP 1-NRF 2分别是缺氧和氧化应激的应激反应机制，有助于胰腺癌的侵袭行为。在胰腺癌细胞和胰腺星状细胞中，这些应激反应机制的关键分子都被激活。这两种因子通过诱导促癌信号及其介质参与癌细胞和星状细胞的相互激活。针对这些途径的治疗干预是有前途的新疗法。本文就缺氧诱导因子-1和KEAP 1-NRF 2在胰腺癌中的作用作一综述。此外，我们还讨论了靶向这些分子治疗胰腺癌的潜力。
Pancreatic cancer progression involves interactions between cancer cells and stromal cells in harsh tumor microenvironments, which are characterized by hypoxia, few nutrients, and oxidative stress. Clinically, cancer cells overcome therapeutic interventions, such as chemotherapy and radiotherapy, to continue to survive. Activation of the adaptation mechanism is required for cancer cell survival under these conditions, and it also contributes to the acquisition of the malignant phenotype. Stromal cells, especially pancreatic stellate cells, play a critical role in the formation of a cancer-promoting microenvironment. We here review the roles of key molecules, hypoxia inducible factor-1 and KEAP1-NRF2, in stress response mechanisms for the adaptation to hypoxia and oxidative stress in pancreatic cancer cells and stellate cells. Various cancer-promoting properties associated with these molecules have been identified, and they might serve as novel therapeutic targets in the future. Pancreatic cancer is intractable due to early progression and resistance to conventional therapy. Dense fibrotic stroma, known as desmoplasia, is a characteristic feature of pancreatic cancer, and develops through the interactions between pancreatic cancer cells and stromal cells, including pancreatic stellate cells. Dense stroma forms harsh tumor microenvironments characterized by hypoxia, few nutrients, and oxidative stress. Pancreatic cancer cells as well as pancreatic stellate cells survive in the harsh microenvironments through the altered expression of signaling molecules, transporters, and metabolic enzymes governed by various stress response mechanisms. Hypoxia inducible factor-1 and KEAP1-NRF2, stress response mechanisms for hypoxia and oxidative stress, respectively, contribute to the aggressive behaviors of pancreatic cancer. These key molecules for stress response mechanisms are activated, both in pancreatic cancer cells and in pancreatic stellate cells. Both factors are involved in the mutual activation of cancer cells and stellate cells, by inducing cancer-promoting signals and their mediators. Therapeutic interventions targeting these pathways are promising approaches for novel therapies. In this review, we summarize the roles of stress response mechanisms, focusing on hypoxia inducible factor-1 and KEAP1-NRF2, in pancreatic cancer. In addition, we discuss the potential of targeting these molecules for the treatment of pancreatic cancer.
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影响因子：
11.2
作者：
Galan-Cobo, Ana;Sitthideatphaiboon, Piyada;Heymach, John, V
通讯作者：
Heymach, John, V
影响因子：
9
作者：
Dai B;Augustine JJ;Kang Y;Roife D;Li X;Deng J;Tan L;Rusling LA;Weinstein JN;Lorenzi PL;Kim MP;Fleming JB
通讯作者：
Fleming JB
影响因子：
5.2
作者：
Carvalho TMA;Di Molfetta D;Greco MR;Koltai T;Alfarouk KO;Reshkin SJ;Cardone RA
通讯作者：
Cardone RA
DOI：
10.1016/j.bbrc.2019.06.096
发表时间：
2019-08-27
影响因子：
3.1
作者：
Cao, X. P.;Cao, Y.;Zhu, Z. M.
通讯作者：
Zhu, Z. M.
影响因子：
2.2
作者：
Eguchi, Daiki;Ikenaga, Naoki;Tanaka, Masao
通讯作者：
Tanaka, Masao