RSPO2 promotes progression of ovarian cancer through dual receptor-mediated FAK/Src signaling activation

R-spondin 2 (RSPO2) drives the potentiation of Wnt signaling and is implicated in tumorigenesis in multiple cancers, but its role in ovarian cancer has not been investigated. Here, we reported that RSPO2 promoted the growth and metastasis of ovarian cancer through the activation of FAK/Src signaling cascades. RSPO2 enhanced the autophosphorylation of FAK and Src through a unique dual receptors mechanism. First, RSPO2-LGR4 interaction prevented the endocytic degradation of LGR4 and promoted LGR4-mediated translocation of Src to the plasma membrane. Second, RSPO2 directly bound to integrin beta 3 as a ligand and enhanced the stability of integrins, and both actions potentiated autoactivation of FAK and/or Src in ovarian cancer cells. RSPO2 expression was increased in ovarian tumors and was associated with poor prognosis in patients. Our study highlights the importance of RSPO2 in ovarian tumor progression and suggests that targeting RSPO2/FAK/Src cascades may constitute potential approaches to inhibit the progression of aggressive ovarian cancer.

Automated summary

RSPO2 promotes the growth and metastasis of ovarian cancer through the activation of FAK/Src signaling cascades. It prevents the endocytic degradation of LGR4 and promotes LGR4-mediated translocation of Src to the plasma membrane. In addition, it directly binds to integrin beta 3 and enhances the stability of integrins. High expression of RSPO2 is associated with poor prognosis in ovarian tumors.