摘要：SummaryEmerging evidence suggests that ADP-ribosylation factor like-4c (Arl4c) may be a potential choice for cancer treatment. However, its role in pancreatic cancer, especially in tumor-stroma interactions and drug resistance, is still unknown. In the current study, we examined the proliferation and drug resistance effect of Arl4c on pancreatic cancer cells. Furthermore, we explored the contribution of Arl4c high expression in pancreatic stellate cell (PSC) activation. We found that high Arl4c expression is associated with cell proliferation, drug resistance, and PSC activation. In detail, Arl4c regulates connective tissue growth factor (CTGF) paracrine, further induces autophagic flux in PSCs, resulting in PSC activation. TGFβ1 secreted by activated PSCs enhances cancer cell stem cell properties via smad2 signaling, further increasing cell drug resistance. YAP is an important mediator of the Arl4c-CTGF loop. Taken together, these results suggest that Arl4c is essential for pancreatic cancer progression and may be an effective therapeutic choice.Graphical abstractDisplay OmittedHighlights•High Arl4c expression is correlated with PSCs activation and drug resistance•Yap-CTGF-mediated autophagy is required for Arl4c-related PSCs activation•Paracrine TGFβ1 of PSCs plays pivotal role in drug resistance of pancreatic cancer cellsBiological sciences; Cell biology; Functional aspects of cell biology; Cancer
