Arl4c promotes the growth and drug resistance of pancreatic cancer by regulating tumor-stromal interactions
Xin Chen,
Yanzhen Zhang,
Weikun Qian,
Liang Han,
Wei Li,
Wanxing Duan,
Zheng Wu,
Zheng Wang,
Qingyong Ma
Affiliations
Xin Chen
Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
Yanzhen Zhang
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
Weikun Qian
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
Liang Han
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
Wei Li
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
Wanxing Duan
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
Zheng Wu
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
Zheng Wang
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
Qingyong Ma
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; Corresponding author
Summary: Emerging 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.
