S100A9 Derived from Chemoembolization-Induced Hypoxia Governs Mitochondrial Function in Hepatocellular Carcinoma Progression.
S100A9 Derived from Chemoembolization-Induced Hypoxia Governs Mitochondrial Function in Hepatocellular Carcinoma Progression.
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DOI：
10.1002/advs.202202206
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发表时间：
2022-10
期刊：
影响因子：
--
通讯作者：
Li B
中科院分区：
文献类型：
--
作者：
Zhong C;Niu Y;Liu W;Yuan Y;Li K;Shi Y;Qiu Z;Li K;Lin Z;Huang Z;Zuo D;Yang Z;Liao Y;Zhang Y;Wang C;Qiu J;He W;Yuan Y;Li B
经动脉化疗栓塞术（TACE）是治疗晚期肝癌的主要方法，但TACE可能会造成缺氧环境，导致治疗后病情迅速恶化。在这里，使用不同模型的高通量测序，S100钙结合蛋白A9（S100 A9）被确定为参与TACE后进展的关键癌基因。S100 A9的缺失或药物抑制显著抑制HCC的生长和转移能力。从机制上讲，TACE通过缺氧诱导因子1α（HIF 1A）介导的途径诱导S100 A9。S100 A9作为一种支架，募集泛素特异性肽酶10和磷酸甘油酸酯家族成员5（PGAM 5）形成三聚体，引起PGAM 5的去泛素化和稳定化，导致线粒体分裂和活性氧产生，从而促进HCC的生长和转移。HCC组织或血清中S100 A9水平越高，HCC患者预后越差。总的来说，本研究将S100 A9确定为TACE后HCC进展的关键驱动因素。靶向S100 A9可能是HCC患者有希望的治疗策略。S100钙结合蛋白-A9（S100 A9）与经动脉化疗栓塞（TACE）后肝细胞癌（HCC）进展相关。肝动脉化疗栓塞可增加肝癌细胞S100 A9的表达。S100 A9促进泛素特异性肽酶-10（USP 10）和磷酸甘油酸酯β家族成员-5（PGAM 5）之间的结合，导致PGAM 5的稳定，从而增加活性氧水平并随后诱导HCC的生长和转移。
Transarterial chemoembolization (TACE) is the major treatment for advanced hepatocellular carcinoma (HCC), but it may cause hypoxic environment, leading to rapid progression after treatment. Here, using high‐throughput sequencing on different models, S100 calcium binding protein A9 (S100A9) is identified as a key oncogene involved in post‐TACE progression. Depletion or pharmacologic inhibition of S100A9 significantly dampens the growth and metastatic ability of HCC. Mechanistically, TACE induces S100A9 via hypoxia‐inducible factor 1α (HIF1A)‐mediated pathway. S100A9 acts as a scaffold recruiting ubiquitin specific peptidase 10 and phosphoglycerate mutase family member 5 (PGAM5) to form a tripolymer, causing the deubiquitination and stabilization of PGAM5, leading to mitochondrial fission and reactive oxygen species production, thereby promoting the growth and metastasis of HCC. Higher S100A9 level in HCC tissue or in serum predicts a worse outcome for HCC patients. Collectively, this study identifies S100A9 as a key driver for post‐TACE HCC progression. Targeting S100A9 may be a promising therapeutic strategy for HCC patients. S100 calcium binding protein‐A9 (S100A9) is associated with post‐transarterial chemoembolization (TACE) hepatocellular carcinoma (HCC) progression. TACE increases the expression of S100A9 in HCC cells. S100A9 promotes binding between ubiquitin specific peptidase‐10 (USP10) and phosphoglycerate mutase family member‐5 (PGAM5), leading to the stabilization of PGAM5, which increases reactive oxygen species levels and subsequently inducing the growth and metastasis of HCC.
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DOI：
10.1002/cac2.12197
发表时间：
2021-10
期刊：
Cancer communications (London, England)
影响因子：
--
作者：
Qiu H;Cao S;Xu R
通讯作者：
Xu R
影响因子：
13.5
作者：
Nemeth, Julia;Stein, Ilan;Hess, Jochen
通讯作者：
Hess, Jochen
影响因子：
11.4
作者：
Cheng, Pinyang;Eksioglu, Erika A.;Wei, Sheng
通讯作者：
Wei, Sheng
DOI：
10.1084/jem.20080132
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cheng P;Corzo CA;Luetteke N;Yu B;Nagaraj S;Bui MM;Ortiz M;Nacken W;Sorg C;Vogl T;Roth J;Gabrilovich DI
通讯作者：
Gabrilovich DI
影响因子：
50.3
作者：
Renz BW;Takahashi R;Tanaka T;Macchini M;Hayakawa Y;Dantes Z;Maurer HC;Chen X;Jiang Z;Westphalen CB;Ilmer M;Valenti G;Mohanta SK;Habenicht AJR;Middelhoff M;Chu T;Nagar K;Tailor Y;Casadei R;Di Marco M;Kleespies A;Friedman RA;Remotti H;Reichert M;Worthley DL;Neumann J;Werner J;Iuga AC;Olive KP;Wang TC
通讯作者：
Wang TC