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Xu, Yanmin; Xu, Huailong; Li, Mingyuan; Wu, Hua; Guo, Yanhe; Chen, Jun; Shan, Juanjuan; Chen, Xuejiao; Shen, Junjie; Ma, Qinghua; Liu, Jingxia; Wang, Meiling; Zhao, Wenxu; Hong, Juan; Qi, Yanan; Yao, Chao; Zhang, Qianzhen; Yang, Zhi; Qian, Cheng; Li, Jianming
Cancer letters, 07/2019, Letnik: 454Journal Article
Patients with advanced hepatocellular carcinoma (HCC) will almost always develop acquired tolerance after sorafenib therapy, and the molecular mechanism of sorafenib tolerance remains poorly characterized. Here, using our established sorafenib-resistant HCC cell and xenograft models, we identified a novel gene, KIAA1199, which was markedly elevated among the differentially expressed genes involved in sorafenib tolerance. Moreover, elevated expression of KIAA1199 was positively correlated with a high risk of recurrence and metastasis and advanced TNM stage in HCC patients. Functionally, loss- and gain-of-function studies showed that KIAA1199 promoted the migration, invasion, and metastasis of sorafenib-resistant HCC cells. Mechanistically, KIAA1199 is required for EGF-induced epithelial-mesenchymal transition (EMT) in sorafenib-resistant HCC cells by aiding in EGFR phosphorylation. In summary, our data uncover KIAA1199 as a novel sorafenib-tolerant promoting gene that plays an indispensable role in maintaining sorafenib-resistant HCC cell metastasis. •Sorafenib-resistant HCC xenografts models were established to illustrate sorafenib resistance in HCC.•KIAA1199 was positively correlated to high risk of recurrence and metastasis in HCC patients.•KIAA1199 enhanced the metastasis of sorafenib-resistant HCC cells by activation of EGF/EGFR-dependent EMT programs.
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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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