ALPL Reduces The Potential Of Migration And Invasion In High Grade Serous Ovarian Cancer Via Down-regulating A FZD2/STAT3 Signaling Pathway

Objective: Previously,ALPL was observed to improve the chemo-response of high grade serous ovarian cancer(HGSOC)cells to paclitaxel as a tumor suppressor gene.Owing to the inverse relationship between ALPL and FIGO stage,this study was designed to explore its role in cell motility of HGSOC and possible mechanism.Methods: The suppressive effects of ALPL on migration and invasion were detected by transwell and wound healing assays in HGSOC cell lines(SKOV3 and HEY)with ALPL overexpressed.Gene Ontology(GO)analysis for the differential genes in SKOV3-ALPL cells from control identified several biological processes(including EMT)correlated with cell motility.And the association of ALPL with a WNT receptor Frizzled2(FZD2)was analyzed from TCGA database,and their role in HGSOC cell motility was investigated.Then we detected the FZD2 expression by IHC assay(Paraffin tissue blocks)in SOC samples(n=90)and compared with contralateral normal tissues in benign ovarian tumor samples(n=40).Results: ALPL overexpression was found to reduce the expression of FZD2,WNT5 A and phosphorylated-STAT3(pSTAT3)in vitro.Similarly,FZD2 knockdown by siRNA could also decrease pSTAT3 expression;whereas administration of recombinant WNT5 A protein could restore FZD2 and pSTAT3 expression.Finally,the relationship of FZD2 expression with poor survival of patients with SOC was also investigated.Conclusion: Our data supports that ALPL might restrict the function of WNT5A-FZD2-STAT3 axis,a non-canonical WNT pathway for promoting EMT progression,which results in attenuated migration and invasion in HGSOC cells and improves survival in patients with SOC.