Feng Zhu

JAK2/ULK1 axis promotes cervical cancer progression by autophagy induction and SRPK1 phosphorylation

Cervical cancer is the most common gynecologic cancer. Autophagy is involved in the progression of CCa. ULK1 is a crucial kinase in autophagy initiation. However, few studies have investigated the role of ULK1 phosphorylation at tyrosine residues in the progression of CCa, and the underlying mechanism remains elusive. In this study, we demonstrated that JAK2 is a novel upstream kinase that phosphorylates ULK1 at the tyrosine site. JAK2 interacts with and phosphorylates ULK1 at Tyr1007. The phosphorylation of ULK1 at Y1007 increases its activity and stability, activates autophagy, and promotes the progression of CCa. We further showed that the phosphorylation of ULK1 at Y1007 is a predictive marker of CCa patient outcome. Furthermore, we identified SRPK1 as a potential downstream substrate of ULK1 to promote the progression of CCa. Our research sheds light on the molecular mechanism of CCa progression, through JAK2/ULK1 axis, and emphasizes the phosphorylation of ULK1 at Y1007 as a predictor of CCa.