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细胞色素 B5 型 A 通过调节 STOML2 相关自噬并促进对芦可替尼的敏感性来减轻 HCC 转移。

Cytochrome B5 type A alleviates HCC metastasis via regulating STOML2 related autophagy and promoting sensitivity to ruxolitinib.

机构信息

Department of Hepatic Surgery, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Department of Hepatobiliary Surgery, Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.

出版信息

Cell Death Dis. 2022 Jul 18;13(7):623. doi: 10.1038/s41419-022-05053-8.

Abstract

The incidence of hepatocellular carcinoma (HCC) is increasing in the world. However, its role and underlying molecular mechanism in HCC progression remain unclear. We found that CYB5A plays a key role in HCC metastasis by inhibiting the JAK1/STAT3 pathway through binding to STOML2. CYB5A combined with STOML2 can predict the outcome of patients. To demonstrate the effect of CYB5A on JAK1 inhibitor function, we applied Ruxolitinib in metastatic tumors with high CYB5A expression and found that it slowed disease progression and prolonged survival in mice. To the best of our knowledge, this study is the first to report the Ruxolitinib effect on the metastatic ability of HCC cells in vivo and in vitro.

摘要

肝细胞癌 (HCC) 的发病率在全球范围内呈上升趋势。然而,其在 HCC 进展中的作用及其潜在的分子机制仍不清楚。我们发现,CYB5A 通过与 STOML2 结合抑制 JAK1/STAT3 通路,在 HCC 转移中发挥关键作用。CYB5A 与 STOML2 结合可预测患者的预后。为了证明 CYB5A 对 JAK1 抑制剂功能的影响,我们在高表达 CYB5A 的转移性肿瘤中应用了鲁索利替尼,发现它能减缓疾病进展并延长小鼠的生存期。据我们所知,这项研究首次报道了鲁索利替尼对 HCC 细胞体内和体外转移能力的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/666b/9293983/bb61d9956163/41419_2022_5053_Fig1_HTML.jpg

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