SPHK 1‐induced autophagy in peritoneal mesothelial cell enhances gastric cancer peritoneal dissemination

Gastric cancer peritoneal dissemination ( GCPD ) has been recognized as the most common form of metastasis in advanced gastric cancer ( GC ), and the survival is pessimistic. The injury of mesothelial cells plays an important role in GCPD . However, its molecular mechanism is not entirely clear. Here, we focused on the sphingosine kinase 1 ( SPHK 1) in human peritoneal mesothelial cells ( HPMC s) which regulates HPMC s autophagy in GCPD progression. Initially, we analyzed SPHK 1 expression immunohistochemically in 120 GC peritoneal tissues, and found high SPHK 1 expression to be significantly associated with LC 3B expression and peritoneal recurrence, leading to poor prognosis. Using a coculture system, we observed that GC cells promoted HPMC s autophagy and this process was inhibited by blocking TGF ‐β1 secreted from GC cells. Autophagic HPMC s induced adhesion and invasion of GC cells. We also confirmed that knockdown of SPHK 1 expression in HPMC s inhibited TGF ‐β1‐induced autophagy. In addition, SPHK 1‐driven autophagy of HPMCs accelerated GC cells occurrence of GCPD in vitro and in vivo. Moreover, we explored the relationship between autophagy and fibrosis in HPMC s, observing that overexpression of SPHK 1 induced HPMC s fibrosis, while the inhibition of autophagy weakened HPMC s fibrosis. Taken together, our results provided new insights for understanding the mechanisms of GCPD and established SPHK 1 as a novel target for GCPD .