Liu Youyi, Liu Lijuan, Zhou Yan, Zhou Ping, Yan Qiujin, Chen Xiaobei, Ding Shuang, Zhu Fan
State Key Laboratory of Virology, Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan, China.
Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, China.
Clin Cancer Res. 2019 Jul 1;25(13):4141-4154. doi: 10.1158/1078-0432.CCR-18-3510. Epub 2019 Mar 27.
Hepatocellular carcinoma (HCC), one of the most common and deadliest malignancies worldwide, has a poor prognosis, owing to its high potential for vascular invasion and metastasis and the lack of biomarkers for early diagnosis. Thus, it must be a crucial factor for investigating therapeutic strategies for HCC to identify the functional molecular targets. Here, we reported a novel chemokine, CKLF1, that might act as a pivotal modulator in the invasion and metastasis of HCC and could serve as an attractive target for cancer therapy.
Bioinformatics analysis, PCR, Western blotting, and IHC were performed to detect the expression of CKLF1 in HCC. The function of CKLF1 was demonstrated by a series of and experiments. Pharmacologic treatment, flow cytometry, and Western blotting were carried out to demonstrate the potential mechanisms of CKLF1.
We proved that CKLF1 was overexpressed in HCC tissues and was related to tumor stage, vascular invasion, and patient survival. Then, functional assays showed that CKLF1 promoted hepatocellular carcinogenesis and metastatic potential. Finally, the IL6/STAT3 signaling pathway was involved in the mechanistic investigation. The results demonstrated that CKLF1 enhanced the progression of HCC and prevented doxorubicin-induced apoptosis through activating the IL6/STAT3 pathway.
These data showed that CKLF1 inhibited apoptosis and promoted malignant transformation through the IL6/STAT3 pathway, and ultimately enhanced the development and metastasis of HCC. Thus, our work revealed that CKLF1 was a significant prognostic factor of HCC and might be a potential molecular therapeutic target for HCC.
肝细胞癌（HCC）是全球最常见且致死率最高的恶性肿瘤之一，预后较差，这归因于其高血管侵袭和转移潜能以及缺乏早期诊断生物标志物。因此，识别功能性分子靶点必定是研究HCC治疗策略的关键因素。在此，我们报道了一种新型趋化因子CKLF1，它可能在HCC的侵袭和转移中起关键调节作用，并可能成为有吸引力的癌症治疗靶点。
进行生物信息学分析、聚合酶链反应（PCR）、蛋白质免疫印迹法（Western blotting）和免疫组化（IHC）以检测CKLF1在HCC中的表达。通过一系列……和……实验证明CKLF1的功能。进行药物治疗、流式细胞术和蛋白质免疫印迹法以阐明CKLF1的潜在机制。
我们证实CKLF1在HCC组织中过表达，且与肿瘤分期、血管侵袭和患者生存率相关。然后，功能分析表明CKLF1促进肝细胞癌发生和转移潜能。最后，白细胞介素6（IL6）/信号转导和转录激活因子3（STAT3）信号通路参与机制研究。结果表明CKLF1通过激活IL6/STAT3通路增强HCC进展并阻止阿霉素诱导的细胞凋亡。
这些数据表明CKLF1通过IL6/STAT3通路抑制细胞凋亡并促进恶性转化，最终增强HCC的发展和转移。因此，我们的研究揭示CKLF1是HCC的一个重要预后因素，可能是HCC潜在的分子治疗靶点。
