Liang Chen, Qin Yi, Zhang Bo, Ji Shunrong, Shi Si, Xu Wenyan, Liu Jiang, Xiang Jinfeng, Liang Dingkong, Hu Qiangsheng, Ni Quanxing, Yu Xianjun, Xu Jin
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Cancer Lett. 2017 Mar 1;388:303-311. doi: 10.1016/j.canlet.2016.12.014. Epub 2016 Dec 23.
Though significant progress has been made in the availability of diagnostic techniques and treatment strategies, pancreatic cancer remains a disease of high mortality rates. Therefore, there is an urgent need for a better understanding of the molecular mechanisms that governs the oncogenesis and metastasis process of pancreatic cancer. In our study, by using the Cancer Genome Atlas (TCGA) dataset analysis, we demonstrated that the small guanosine triphosphatase (GTPase) ADP-ribosylation factor 6 (ARF6) serves as a biomarker for predicting prognosis of pancreatic cancer. In vitro studies demonstrated that silencing ARF6 expression reduced cell proliferation and attenuated the Warburg effect. Moreover, we observed that ARF6 was a downstream target of Kras/ERK signaling pathway, and the strong correlation of expression between Kras and ARF6 in the TCGA dataset further confirmed this observation. Taken together, our novel findings suggest ARF6, a target of mutant Kras, may promote pancreatic cancer development by enhancing the Warburg effect.
尽管在诊断技术和治疗策略的可用性方面已经取得了重大进展，但胰腺癌仍然是一种死亡率很高的疾病。因此，迫切需要更好地了解控制胰腺癌发生和转移过程的分子机制。在我们的研究中，通过使用癌症基因组图谱（TCGA）数据集分析，我们证明小GTP酶（GTPase）ADP核糖基化因子6（ARF6）可作为预测胰腺癌预后的生物标志物。体外研究表明，沉默ARF6表达可减少细胞增殖并减弱瓦伯格效应。此外，我们观察到ARF6是Kras/ERK信号通路的下游靶点，TCGA数据集中Kras与ARF6表达之间的强相关性进一步证实了这一观察结果。综上所述，我们的新发现表明，作为突变型Kras靶点的ARF6可能通过增强瓦伯格效应促进胰腺癌的发展。
