AHA1 upregulates IDH1 and metabolic activity to promote growth and metastasis and predicts prognosis in osteosarcoma.
AHA1 upregulates IDH1 and metabolic activity to promote growth and metastasis and predicts prognosis in osteosarcoma.
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AHA1 上调 IDH1 和代谢活性以促进骨肉瘤的生长和转移并预测预后
DOI：
10.1038/s41392-020-00387-1
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发表时间：
2021-01-20
影响因子：
39.3
通讯作者：
Shi Z
中科院分区：
文献类型：
--
作者：
Zheng D;Liu W;Xie W;Huang G;Jiang Q;Yang Y;Huang J;Xing Z;Yuan M;Wei M;Li Y;Yin J;Shen J;Shi Z
骨肉瘤是儿童和青少年最常见的原发性恶性骨肿瘤。虽然HSP 90 ATP酶活性激活因子1（AHA 1）是一个潜在的癌基因，但其在骨肉瘤进展中的作用仍不清楚。由于代谢重编程参与肿瘤发生和癌症转移，因此AHA 1与癌症代谢的关系尚不清楚。本研究发现AHA 1在骨肉瘤中显著过表达，并与骨肉瘤患者的预后有关。AHA 1在体内外均能促进骨肉瘤的生长和转移。从机制上讲，AHA 1上调代谢活性以满足骨肉瘤中细胞的生物能量需求。值得注意的是，我们鉴定了异柠檬酸脱氢酶1（IDH 1）是Hsp 90-AHA 1的新型客户蛋白。骨肉瘤中IDH 1与AHA 1蛋白表达呈正相关。IDH 1过表达可部分逆转AHA 1基因敲减对骨肉瘤细胞生长和迁移的影响。此外，高水平的IDH 1也与骨肉瘤患者的预后不良有关。这项研究表明，AHA 1正调控IDH 1和代谢活性，以促进骨肉瘤的生长和转移，这为骨肉瘤患者提供了新的预后生物标志物和有希望的治疗靶点。
Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. Although activator of HSP90 ATPase activity 1 (AHA1) is reported to be a potential oncogene, its role in osteosarcoma progression remains largely unclear. Since metabolism reprogramming is involved in tumorigenesis and cancer metastasis, the relationship between AHA1 and cancer metabolism is unknown. In this study, we found that AHA1 is significantly overexpressed in osteosarcoma and related to the prognosis of osteosarcoma patients. AHA1 promotes the growth and metastasis of osteosarcoma both in vitro and in vivo. Mechanistically, AHA1 upregulates the metabolic activity to meet cellular bioenergetic needs in osteosarcoma. Notably, we identified that isocitrate dehydrogenase 1 (IDH1) is a novel client protein of Hsp90-AHA1. Furthermore, the IDH1 protein level was positively correlated with AHA1 in osteosarcoma. And IDH1 overexpression could partially reverse the effect of AHA1 knockdown on cell growth and migration of osteosarcoma. Moreover, high IDH1 level was also associated with poor prognosis of osteosarcoma patients. This study demonstrates that AHA1 positively regulates IDH1 and metabolic activity to promote osteosarcoma growth and metastasis, which provides novel prognostic biomarkers and promising therapeutic targets for osteosarcoma patients.
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影响因子：
4.3
作者：
Pascual G;Domínguez D;Benitah SA
通讯作者：
Benitah SA
影响因子：
6.4
作者：
McCleese, Jennifer K.;Bear, Misty D.;London, Cheryl A.
通讯作者：
London, Cheryl A.
影响因子：
4.8
作者：
Tripathi, Vishwadeepak;Darnauer, Stefanie;Obermann, Wolfgang M. J.
通讯作者：
Obermann, Wolfgang M. J.
影响因子：
7.4
作者：
Lepvrier, Eleonore;Mollintraffort, Laura;Garnier, Cyrille
通讯作者：
Garnier, Cyrille
影响因子：
64.8
作者：
Gao, Ping;Tchernyshyov, Irina;Chang, Tsung-Cheng;Lee, Yun-Sil;Kita, Kayoko;Ochi, Takafumi;Zeller, Karen I.;De Marzo, Angelo M.;Van Eyk, Jennifer E.;Mendell, Joshua T.;Dang, Chi V.
通讯作者：
Dang, Chi V.