CD44 potentiates hepatocellular carcinoma migration and extrahepatic metastases via the AKT/ERK signaling CXCR4 axis.
CD44 potentiates hepatocellular carcinoma migration and extrahepatic metastases via the AKT/ERK signaling CXCR4 axis.
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CD44 通过 AKT/ERK 信号 CXCR4 轴增强肝细胞癌迁移和肝外转移
DOI：
10.21037/atm-22-2482
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发表时间：
2022-06
影响因子：
--
通讯作者：
Guo, Lei
中科院分区：
文献类型：
--
作者：
Xie, Peiyi;Yan, Jiuliang;Wu, Mengyuan;Li, Hui;Chen, Zheng;Yu, Mincheng;Zhang, Bo;Chen, Lingli;Jin, Lei;Zhou, Binghai;Li, Xiaoqiang;Xiao, Yongsheng;Xu, Yongfeng;Long, Jiang;Zhang, Jubo;Guo, Lei
关键词：
细胞粘附分子分化簇44（CD 44）在癌细胞的局部侵袭、浸润、迁移和转移灶的形成中起重要作用。然而，关于CD 44如何调节肝细胞癌（HCC）肝外转移（EHM）的潜在机制知之甚少。采用免疫印迹法和免疫组化法检测肝癌组织和细胞系中CD 44的表达。通过功能获得和功能丧失试验，我们研究了CD 44在体外和体内调节HCC细胞生长和转移中的致癌作用。为了确定潜在的机制，我们采用定量实时聚合酶链反应，和蛋白质印迹。在这项研究中，CD 44在HCC细胞和表现出高恶性潜能的HCC患者标本中高度表达。CD 44过表达的HCC患者的总生存率（OS）较差，累积复发率高于CD 44低表达者。我们的体外和体内实验表明，CD 44下调减少HCC细胞集落形成、迁移和侵袭，以及HCC肿瘤的生长和转移，并且CD 44的促转移作用是由蛋白激酶B（AKT）/细胞外信号调节激酶（ERK）信号传导-趋化因子受体C-X-C趋化因子受体4型（CXCR 4）轴介导的。报道的CD 44诱导CXCR 4表达和增加肿瘤侵袭和转移到远处器官的倾向的能力与HCC的侵袭性临床特征一致。CD 44可能是EHM未来的治疗靶点。
Cell adhesion molecule cluster of differentiation 44 (CD44) plays a significant role in cancer cell local invasion, intravasation, migration, and the establishment of metastatic lesions. However, little is known about the underlying mechanism of how CD44 regulates hepatocellular carcinoma (HCC) extrahepatic metastasis (EHM). The expression of CD44 in HCC tissues and cell lines was detected through western blot and immunohistochemistry (IHC). Through gain- and loss-of-function assays, we examined the oncogenic roles of CD44 in regulating HCC cell growth and metastasis in vitro and in vivo. To identify the potential mechanism, we employed quantitative real-time polymerase chain reaction, and western blot. In this study, CD44 was highly expressed in HCC cells and HCC-patient specimens that exhibited high malignancy potential. The overall survival (OS) was worse and the cumulative recurrence rate was higher in HCC patients with CD44 overexpression than those with low levels of CD44 expression. Our in-vitro and in-vivo experiments showed that CD44 downregulation reduced HCC cell colony formation, migration, and invasion, and HCC tumor growth and metastasis, and that the pro-metastasis effect of CD44 was mediated by the protein kinase B (AKT)/extracellular signal-regulated kinase (ERK) signaling-chemokine receptor C-X-C chemokine receptor type 4 (CXCR4) axis. The reported capacity of CD44 to induce CXCR4 expression and increase the propensity of tumors to invade and metastasize to distant organs is consistent with the aggressive clinical characteristics of HCCs. CD44 could represent a future therapeutic target for EHM.
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影响因子：
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