Wnt signaling in ovarian tumorigenesis

Abstract

Data are emerging implicating Wnt signaling in ovarian tumorigenesis. We sought to review the current literature on the subject and discuss the pathway's potential role as a prognostic marker and therapeutic target. We conducted a systematic literature review of studies investigating the association between Wnt signaling and ovarian cancer. Search strategies included online searching of the MEDLINE database and hand searching of relevant publications and reviews. Additional reports were collected by systematically reviewing all references from retrieved papers. Twenty-nine papers were identified that directly investigate Wnt signaling and ovarian cancer. Mutations in the CTNNB1 gene that codes for beta-catenin, the key effector in the pathway, are directly linked to carcinogenic transformation but are mostly found in ovarian endometrioid adenocarcinomas, a histologic subtype of epithelial ovarian cancer. These mutations, along with others, lead to deregulation of the pathway and transcription of target genes. Differences in various intra- and extracellular components of the Wnt pathway have been demonstrated between normal ovarian and cancer cell lines and between benign tissue and ovarian cancer. These differences implicate Wnt signaling in the molecular events that lead to ovarian cancer development despite the fact that gene mutations are uncommon. The data suggest that Wnt signaling plays a role in ovarian tumorigenesis. The exact mechanisms by which this occurs need to be further elucidated. Wnt signaling is probably involved via multiple, diverse mechanisms. Further research in this area is warranted.

Figure 1

Schema of the Wnt signaling pathways.

Figure 2

Three of the screened compounds.