Overexpression of HACE1 in gastric cancer inhibits tumor aggressiveness by impeding cell proliferation and migration.
Overexpression of HACE1 in gastric cancer inhibits tumor aggressiveness by impeding cell proliferation and migration.
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胃癌中 HACE1 的过度表达通过阻碍细胞增殖和迁移来抑制肿瘤侵袭性
DOI：
10.1002/cam4.1496
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发表时间：
2018-06
期刊：
影响因子：
4
通讯作者：
Gao H
中科院分区：
文献类型：
--
作者：
Chen YL;Li DP;Jiang HY;Yang Y;Xu LL;Zhang SC;Gao H
HACE1 E3连接酶在几种癌症中被发现下调，但其在肿瘤调节中的作用尚不清楚。本研究旨在探讨HACE1在胃肿瘤发生中的具体作用及其潜在机制。胃癌组织中HACE1的表达明显低于癌旁正常组织（P < 0.001）。其在胃癌组织中的表达水平与肿瘤病理分化呈负相关（P = 0.019）。在伴有TNM I - IIIa的胃癌患者中，HACE1蛋白水平较低的患者总生存率较低（P = 0.025）。体内和体外研究表明，过表达HACE1可抑制肿瘤的增殖和迁移，增强细胞凋亡。此外，HACE1的异位表达下调了β - catenin蛋白水平，抑制了Wnt/β - catenin信号通路的活性。当我们过表达失活的HACE1 - deltaHECT时，所有细胞功能都被取消。总之，我们证明了HACE1 E3连接酶在胃肿瘤发生中起抑制作用，并抑制了Wnt/β‐catenin信号通路的活性。在胃癌早期规避HACE1的下降可能会阻碍胃癌的发生和恶性进程。
HACE1 E3 ligase was discovered to be down‐regulated in several cancers while its role in regulating tumors was merely understood. This study aimed to explore the specific effect of HACE1 played in gastric tumorigenesis and its potential mechanism. HACE1's expression was found significantly lower in gastric cancer tissues compared with the adjacent normal tissues (P < 0.001). Its protein level in gastric cancer negatively correlated to tumor pathological differentiation (P = 0.019). And in gastric cancer patients with TNM I‐IIIa, those with lower HACE1 protein level had poorer overall survival (P = 0.025). Studies, in vivo and in vitro, showed that overexpressing HACE1 inhibited tumor proliferation and migration, and enhanced cell apoptosis. Besides, ectopic expression of HACE1 down‐regulated the protein level of β‐catenin and inhibited the activity of the Wnt/β‐catenin signaling pathway. All the cellular functions were abolished when we overexpressed inactive HACE1‐deltaHECT. Above all, we demonstrated that HACE1 E3 ligase played a suppressive role in gastric tumorigenesis and inhibited the activity of the Wnt/β‐catenin signaling pathway. Circumventing the decline of HACE1 in early stage of carcinoma may impede the tumorigenesis and malignant process of gastric cancer.
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影响因子：
2.7
作者：
Bouzelfen, Abdelilah;Alcantara, Marion;Jardin, Fabrice
通讯作者：
Jardin, Fabrice
影响因子：
50.3
作者：
Liu Z;Chen P;Gao H;Gu Y;Yang J;Peng H;Xu X;Wang H;Yang M;Liu X;Fan L;Chen S;Zhou J;Sun Y;Ruan K;Cheng S;Komatsu M;White E;Li L;Ji H;Finley D;Hu R
通讯作者：
Hu R
影响因子：
254.7
作者：
Torre, Lindsey A.;Bray, Freddie;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
6
作者：
Kuecuek, Can;Hu, Xiaozhou;Chan, Wing C.
通讯作者：
Chan, Wing C.
肿瘤HACE1是TNFR1介导的细胞命运的关键调节剂。
影响因子：
8.8
作者：
Tortola L;Nitsch R;Bertrand MJM;Kogler M;Redouane Y;Kozieradzki I;Uribesalgo I;Fennell LM;Daugaard M;Klug H;Wirnsberger G;Wimmer R;Perlot T;Sarao R;Rao S;Hanada T;Takahashi N;Kernbauer E;Demiröz D;Lang M;Superti-Furga G;Decker T;Pichler A;Ikeda F;Kroemer G;Vandenabeele P;Sorensen PH;Penninger JM
通讯作者：
Penninger JM