Metabolic implications of hypoxia and pseudohypoxia in pheochromocytoma and paraganglioma.
Metabolic implications of hypoxia and pseudohypoxia in pheochromocytoma and paraganglioma.
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DOI：
10.1007/s00441-018-2801-6
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发表时间：
2018-05
影响因子：
3.6
通讯作者：
Tennant DA
中科院分区：
文献类型：
--
作者：
Kluckova K;Tennant DA
缺氧是癌症发病机制的关键驱动因素，直接诱导恶性表型，如上皮间质转化、干细胞样特征和代谢转化。然而，在没有缺氧的情况下，在癌症中经常观察到与缺氧相关的表型，这种表型被称为假性缺氧，这种表型在特定的肿瘤类型中得到了很好的记录，包括副神经节瘤/嗜铬细胞瘤（PPGL）。大约 40% 的 PPGL 肿瘤在许多易感基因之一中携带种系突变，其中在琥珀酸脱氢酶 (SDH) 或 von Hippel-Lindau (VHL) 基因中发现的突变表现出强烈的假缺氧表型。 SDH 突变具有致癌性，会在选定的组织亚群中形成肿瘤，但其原因仍然难以捉摸。尽管琥珀酸水平升高会导致缺氧样信号传导增加，但 SDH 突变 PPGL 中的其他表型也越来越被人们所认识，例如 DNA 高甲基化。此外，最近公布的 SDH 缺陷细胞代谢重新布线的变化可能有助于未来破译 SDH 与癌症相关的作用。在这篇综述中，我们将讨论 SDH 故障可能产生的各种影响及其对癌症发展的影响。
Hypoxia is a critical driver of cancer pathogenesis, directly inducing malignant phenotypes such as epithelial-mesenchymal transition, stem cell-like characteristics and metabolic transformation. However, hypoxia-associated phenotypes are often observed in cancer in the absence of hypoxia, a phenotype known as pseudohypoxia, which is very well documented in specific tumour types, including in paraganglioma/pheochromocytoma (PPGL). Approximately 40% of the PPGL tumours carry a germ line mutation in one of a number of susceptibility genes of which those that are found in succinate dehydrogenase (SDH) or in von Hippel-Lindau (VHL) genes manifest a strong pseudohypoxic phenotype. Mutations in SDH are oncogenic, forming tumours in a select subset of tissues, but the cause for this remains elusive. Although elevated succinate levels lead to increase in hypoxia-like signalling, there are other phenotypes that are being increasingly recognised in SDH-mutated PPGL, such as DNA hypermethylation. Further, recently unveiled changes in metabolic re-wiring of SDH-deficient cells might help to decipher cancer related roles of SDH in the future. In this review, we will discuss the various implications that the malfunctioning SDH can have and its impact on cancer development.
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影响因子：
16.6
作者：
Bailey ST;Smith AM;Kardos J;Wobker SE;Wilson HL;Krishnan B;Saito R;Lee HJ;Zhang J;Eaton SC;Williams LA;Manocha U;Peters DJ;Pan X;Carroll TJ;Felsher DW;Walter V;Zhang Q;Parker JS;Yeh JJ;Moffitt RA;Leung JY;Kim WY
通讯作者：
Kim WY
影响因子：
3.5
作者：
Castro-Vega, Luis Jaime;Buffet, Alexandre;Gimenez-Roqueplo, Anne-Paule
通讯作者：
Gimenez-Roqueplo, Anne-Paule
影响因子：
64.8
作者：
Chouchani, Edward T.;Pell, Victoria R.;Gaude, Edoardo;Aksentijevic, Dunja;Sundier, Stephanie Y.;Robb, Ellen L.;Logan, Angela;Nadtochiy, Sergiy M.;Ord, Emily N. J.;Smith, Anthony C.;Eyassu, Filmon;Shirley, Rachel;Hu, Chou-Hui;Dare, Anna J.;James, Andrew M.;Rogatti, Sebastian;Hartley, Richard C.;Eaton, Simon;Costa, Ana S. H.;Brookes, Paul S.;Davidson, Sean M.;Duchen, Michael R.;Saeb-Parsy, Kourosh;Shattock, Michael J.;Robinson, Alan J.;Work, Lorraine M.;Frezza, Christian;Krieg, Thomas;Murphy, Michael P.
通讯作者：
Murphy, Michael P.
影响因子：
9.8
作者：
Astuti, D;Latif, F;Maher, ER
通讯作者：
Maher, ER
影响因子：
3.5
作者：
Comino-Mendez, Inaki;de Cubas, Aguirre A.;Cascon, Alberto
通讯作者：
Cascon, Alberto