Rictor promotes cell migration and actin polymerization through regulating ABLIM1 phosphorylation in Hepatocellular Carcinoma.
Rictor promotes cell migration and actin polymerization through regulating ABLIM1 phosphorylation in Hepatocellular Carcinoma.
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Rictor 通过调节肝细胞癌中 ABLIM1 磷酸化促进细胞迁移和肌动蛋白聚合
DOI：
10.7150/ijbs.46285
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发表时间：
2020
影响因子：
9.2
通讯作者：
Kong R
中科院分区：
文献类型：
--
作者：
Dong X;Feng M;Yang H;Liu H;Guo H;Gao X;Liu Y;Liu R;Zhang N;Chen R;Kong R
肝细胞癌（HCC）是最凶险的恶性肿瘤之一，由于其侵袭性和转移性扩散，常常在晚期诊断出来。新出现的证据表明，作为mTORC2的独特成分，Rictor在细胞迁移中起作用，因为它在包括HCC在内的各种癌症中失调。然而，其潜在的分子机制尚未被很好地表征。在这里，对组织阵列面板的评估和生物信息学分析显示，Rictor在HCC组织中高度表达。此外，Rictor表达的增加预示着HCC患者的生存率较差。Rictor敲低显著抑制细胞迁移和肌动蛋白聚合，从而导致MKL1的核积累减少，随后SRF/MKL1依赖性基因转录，即Arp3和c-Fos失活。在机制上，我们确定ABLIM1是以前未知的Rictor磷酸化靶点。在HCC细胞中，Rictor与ABLIM1相互作用并调节其丝氨酸磷酸化。我们产生了ABLIM1敲除肝癌细胞系，其中Ser 214和Ser 431残基的显性负突变抑制了ABLIM1介导的肌动蛋白聚合和MKL1信号通路。综上所述，Rictor诱导ABLIM1磷酸化在HCC细胞中控制肌动蛋白聚合中起重要作用。
As one of the most ominous malignancies, hepatocellular carcinoma (HCC) is frequently diagnosed at an advanced stage, owing to its aggressive invasion and metastatic spread. Emerging evidence has demonstrated that Rictor, as a unique component of the mTORC2, plays a role in cell migration, as it is dysregulated in various cancers, including HCC. However, the underlying molecular mechanism has not been well-characterized. Here, evaluation on a tissue-array panel and bioinformatics analysis revealed that Rictor is highly expressed in HCC tissues. Moreover, increased Rictor expression predicts poor survival of HCC patients. Rictor knockdown significantly suppressed cell migration and actin polymerization, thereby leading to decreased nuclear accumulation of MKL1 and subsequent inactivation of SRF/MKL1-dependent gene transcription, i.e. Arp3 and c-Fos. Mechanistically, we identified ABLIM1 as a previously unknown phosphorylation target of Rictor. Rictor interacts with ABLIM1 and regulates its serine phosphorylation in HCC cells. We generated ABLIM1 knockout cell lines of HCC, in which dominant negative mutations of Ser 214 and Ser 431 residues inhibited the ABLIM1-mediated actin polymerization and the MKL1 signaling pathway. Overall, ABLIM1 phosphorylation induced by Rictor plays an important role in controlling actin polymerization in HCC cells.
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各种各样的癌症相关MTOR突变是过度激活的，可以预测雷帕霉素的敏感性。
影响因子：
28.2
作者：
Grabiner BC;Nardi V;Birsoy K;Possemato R;Shen K;Sinha S;Jordan A;Beck AH;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
21.3
作者：
Er EE;Valiente M;Ganesh K;Zou Y;Agrawal S;Hu J;Griscom B;Rosenblum M;Boire A;Brogi E;Giancotti FG;Schachner M;Malladi S;Massagué J
通讯作者：
Massagué J
影响因子：
37.3
作者：
Jebali A;Dumaz N
通讯作者：
Dumaz N
影响因子：
21.3
作者：
Potter, CJ;Pedraza, LG;Xu, T
通讯作者：
Xu, T
半导体 α-Ag2S 的延性变形机制
影响因子：
9.7
作者：
Li, Guodong;An, Qi;Snyder, G. Jeffrey
通讯作者：
Snyder, G. Jeffrey