Down-regulation of MYH10 driven by chromosome 17p13.1 deletion promotes hepatocellular carcinoma metastasis through activation of the EGFR pathway.
Down-regulation of MYH10 driven by chromosome 17p13.1 deletion promotes hepatocellular carcinoma metastasis through activation of the EGFR pathway.
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DOI：
10.1111/jcmm.17036
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发表时间：
2021-12
影响因子：
5.3
通讯作者：
Zhou G
中科院分区：
文献类型：
--
作者：
Jin Q;Cheng M;Xia X;Han Y;Zhang J;Cao P;Zhou G
体细胞拷贝数改变（CNAs）是癌症的基因组标志。其中，染色体17p13.1缺失在肝细胞癌（HCC）中复发。在这里，利用整合组学分析，我们在17p13.1，肌球蛋白重链10 （MYH10）中筛选了一个新的肿瘤抑制基因。我们观察到原发性HCC组织中MYH10的频繁缺失（约38%）和显著下调。MYH10缺失或表达降低是HCC患者预后不良的潜在指标。敲低MYH10可显著促进HCC细胞在体外的迁移和侵袭，而过表达MYH10则相反。此外，抑制MYH10可显著增强体内HCC转移。我们初步阐明了MYH10缺失通过促进EGFR通路激活促进HCC转移的机制。总之，我们的研究表明，MYH10作为17p13缺失的候选靶基因，可以作为肿瘤抑制因子，并可能作为HCC患者的潜在预后指标。
Somatic copy number alterations (CNAs) are a genomic hallmark of cancers. Among them, the chromosome 17p13.1 deletions are recurrent in hepatocellular carcinoma (HCC). Here, utilizing an integrative omics analysis, we screened out a novel tumour suppressor gene within 17p13.1, myosin heavy chain 10 (MYH10). We observed frequent deletions (~38%) and significant down‐regulation of MYH10 in primary HCC tissues. Deletion or decreased expression of MYH10 was a potential indicator of poor outcomes in HCC patients. Knockdown of MYH10 significantly promotes HCC cell migration and invasion in vitro, and overexpression of MYH10 exhibits opposite effects. Further, inhibition of MYH10 markedly potentiates HCC metastasis in vivo. We preliminarily elucidated the mechanism by which loss of MYH10 promotes HCC metastasis by facilitating EGFR pathway activation. In conclusion, our study suggests that MYH10, a candidate target gene for 17p13 deletion, acts as a tumour suppressor and may serve as a potential prognostic indicator for HCC patients.
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影响因子：
64.5
作者：
Davoli T;Xu AW;Mengwasser KE;Sack LM;Yoon JC;Park PJ;Elledge SJ
通讯作者：
Elledge SJ
影响因子：
3.9
作者：
Liu, Wenya;Cai, Tonghui;Jiang, Qingping
通讯作者：
Jiang, Qingping
DOI：
10.1038/nrm2786
发表时间：
2009-11
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
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影响因子：
4.5
作者：
Ridge LA;Mitchell K;Al-Anbaki A;Shaikh Qureshi WM;Stephen LA;Tenin G;Lu Y;Lupu IE;Clowes C;Robertson A;Barnes E;Wright JA;Keavney B;Ehler E;Lovell SC;Kadler KE;Hentges KE
通讯作者：
Hentges KE
影响因子：
11.2
作者：
Betapudi, Venkaiah;Licate, Lucila S.;Egelhoff, Thomas T.
通讯作者：
Egelhoff, Thomas T.