Donghua Geng1, Huiying Wu2. 1. Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China. 2. Department of Nursing, Shengjing Hospital of China Medical University, Shenyang, China.
Abstract
Background: ADP ribosylation factor 6 (ARF6) is a member of the Rat sarcoma virus (RAS) superfamily that is involved in the regulation of vesicular trafficking, membrane lipid remodeling, and signaling pathways. Our earlier work discovered that ARF6, as a downstream effector of the Kirsten rat sarcoma viral oncogene (Kras)/extracellular signal-regulated kinases (ERK) signaling pathway, may increase proliferation and induce the Warburg effect in gastric cancer (GC) cells. Additionally, ARF6 appears to be a potential biomarker for predicting the prognosis of GC. Ferroptosis has recently been described as a type of nonapoptotic iron-dependent cell death that is strongly associated with the Kras mutation. Therefore, it is critical to continue investigating the link between ARF6 and ferroptosis. Methods: We first created ARF6 silenced cancer cell lines with lentivirus transfection. The knockdown efficiency was confirmed through quantitative polymerase chain reaction (qPCR) and western blotting. Subsequently, we used Cell Counting Kit-8 (CCK-8) and malondialdehyde (MDA) assay for lipid peroxidation measurement. Following this, qPCR and western blotting were conducted to clarify the mechanism involved. Finally, immunohistochemistry was used to stain human GC samples. Results: Our findings established that, whereas ARF6 did not directly regulate lipid peroxidation, it did render GC cells susceptible to oxidative stress, particularly erastin-induced lipid peroxidation. Additionally, our research demonstrated that ARF6 may control capecitabine resistance via several routes. Conclusions: ARF6 may play a critical role in the development of GC. 2022 Journal of Gastrointestinal Oncology. All rights reserved.
Background: ADP ribosylation factor 6 (ARF6) is a member of the Rat sarcoma virus (RAS) superfamily that is involved in the regulation of vesicular trafficking, membrane lipid remodeling, and signaling pathways. Our earlier work discovered that ARF6, as a downstream effector of the Kirsten rat sarcoma viral oncogene (Kras)/extracellular signal-regulated kinases (ERK) signaling pathway, may increase proliferation and induce the Warburg effect in gastric cancer (GC) cells. Additionally, ARF6 appears to be a potential biomarker for predicting the prognosis of GC. Ferroptosis has recently been described as a type of nonapoptotic iron-dependent cell death that is strongly associated with the Kras mutation. Therefore, it is critical to continue investigating the link between ARF6 and ferroptosis. Methods: We first created ARF6 silenced cancer cell lines with lentivirus transfection. The knockdown efficiency was confirmed through quantitative polymerase chain reaction (qPCR) and western blotting. Subsequently, we used Cell Counting Kit-8 (CCK-8) and malondialdehyde (MDA) assay for lipid peroxidation measurement. Following this, qPCR and western blotting were conducted to clarify the mechanism involved. Finally, immunohistochemistry was used to stain human GC samples. Results: Our findings established that, whereas ARF6 did not directly regulate lipid peroxidation, it did render GC cells susceptible to oxidative stress, particularly erastin-induced lipid peroxidation. Additionally, our research demonstrated that ARF6 may control capecitabine resistance via several routes. Conclusions: ARF6 may play a critical role in the development of GC. 2022 Journal of Gastrointestinal Oncology. All rights reserved.
Authors: Jose Pedro Friedmann Angeli; Manuela Schneider; Bettina Proneth; Yulia Y Tyurina; Vladimir A Tyurin; Victoria J Hammond; Nadja Herbach; Michaela Aichler; Axel Walch; Elke Eggenhofer; Devaraj Basavarajappa; Olof Rådmark; Sho Kobayashi; Tobias Seibt; Heike Beck; Frauke Neff; Irene Esposito; Rüdiger Wanke; Heidi Förster; Olena Yefremova; Marc Heinrichmeyer; Georg W Bornkamm; Edward K Geissler; Stephen B Thomas; Brent R Stockwell; Valerie B O'Donnell; Valerian E Kagan; Joel A Schick; Marcus Conrad Journal: Nat Cell Biol Date: 2014-11-17 Impact factor: 28.824
Authors: Wan Seok Yang; Rohitha SriRamaratnam; Matthew E Welsch; Kenichi Shimada; Rachid Skouta; Vasanthi S Viswanathan; Jaime H Cheah; Paul A Clemons; Alykhan F Shamji; Clary B Clish; Lewis M Brown; Albert W Girotti; Virginia W Cornish; Stuart L Schreiber; Brent R Stockwell Journal: Cell Date: 2014-01-16 Impact factor: 41.582