2. Academic Validation
  3. Abrogation of ARF6 promotes RSL3-induced ferroptosis and mitigates gemcitabine resistance in pancreatic cancer cells

Abrogation of ARF6 promotes RSL3-induced ferroptosis and mitigates gemcitabine resistance in pancreatic cancer cells

  • Am J Cancer Res. 2020 Apr 1;10(4):1182-1193.
Zeng Ye 1 2 3 4,  Qiangsheng Hu 1 2 3 4,  Qifeng Zhuo 1 2 3 4,  Yuemeng Zhu 5,  Guixiong Fan 1 2 3 4,  Mengqi Liu 1 2 3 4,  Qiqing Sun 1 2 3 4,  Zheng Zhang 1 2 3 4,  Wensheng Liu 1 2 3 4,  Wenyan Xu 1 2 3 4,  Shunrong Ji 1 2 3 4,  Xianjun Yu 1 2 3 4,  Xiaowu Xu 1 2 3 4,  Yi Qin 1 2 3 4
Affiliations

Affiliations

  • 1 Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center Shanghai, China.
  • 2 Department of Oncology, Shanghai Medical College, Fudan University Shanghai, China.
  • 3 Shanghai Pancreatic Cancer Institute Shanghai, China.
  • 4 Pancreatic Cancer Institute, Fudan University Shanghai, China.
  • 5 Department of Gynecology, Zhongshan-Xuhui Hospital Affiliated to Fudan University Shanghai, China.
PMID: 32368394
Abstract

ADP Ribosylation Factor 6 (ARF6) is a part of the Ras superfamily and regulates vesicular trafficking, remodeling of membrane lipids, and signaling pathways. Our previous study has found that ARF6, functioned as a downstream of Kras/ERK signaling pathway, could promote proliferation and Warburg effect in pancreatic Cancer cells. Moreover, ARF6 is promising to be a biomarker for predicting prognosis of pancreatic Cancer. Ferroptosis is a new defined iron-dependent form of nonapoptotic cell death, which is closely related to Kras mutation. Therefore, it is urgent to further explore the relationship between ARF6 and Ferroptosis. Our study demonstrated that ARF6 did not directly regulate lipid peroxidation, but endowed pancreatic Cancer cells to a status that is sensitive to oxidative stress, especially RSL3-induced lipid peroxidation. Further study revealed that ARF6 could also regulate gemcitabine resistance via multiple pathways. In conclusion, ARF6 has a profound effect on pancreatic Cancer development.

Keywords

ACSL4; ARF6; Ferroptosis; gemcitabine; pancreatic cancer.

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