ARF6, induced by mutant Kras, promotes proliferation and Warburg effect in pancreatic cancer

Abstract 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 oncogenesi...

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Bibliographic Details
Published in:Cancer letters 2017-03, Vol.388, p.303-311
Main Authors: 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
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Adenocarcinoma - pathology
ADP-ribosylation factor 6
ADP-Ribosylation Factors - genetics
Animals
c-Myc
Carcinoma, Pancreatic Ductal - genetics
Carcinoma, Pancreatic Ductal - pathology
Cell growth
Cell Line, Tumor
Cell Proliferation
Genes
Genes, ras - genetics
Hematology, Oncology and Palliative Medicine
Humans
Immunoglobulins
Kinases
Kras/ERK axis
Medical research
Metabolism
Pancreatic cancer
Prognosis
Proteins
Signal Transduction
Transfection
Warburg effect
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Summary:Abstract 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.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2016.12.014