Wnt11 alters integrin and cadherin expression by ovarian cancer spheroids and inhibits tumorigenesis and metastasis

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The present study investigated the role of Wnt11 in multicellular tumor spheroid-like structures (MCTS) ovarian cancer cell proliferation, migration and invasion in vitro and in vivo tumorigenesis and metastasis in xenograft nude mice model. Moreover, samples from human serous ovarian cancer (SOC) were used to assess the association of Wnt11 with integrins and cadherins. The data showed that Wnt11 overexpressing SKOV-3 cells became more compact accompanied by increased expression of E-and N-cadherin and lower expression of EpCAM and CD44. The α5, β2, β3 and β6 integrin subunits expression levels were significantly reduced in Wnt11 overexpressing cells accompanied with significantly reduced disaggregation of Wnt11 overexpressing SKOV-3 MCTS on ECM components. Moreover, Wnt11 overexpressing SKOV-3 MCTS showed decreased migration, invasion as well as no tumor growth and metastasis in vivo. We found that Wnt11 significantly and negatively correlated with ITGB2, ITGB6, and EpCAM and positively with CDH-1 in high-grade SOC specimens. Our results suggest that Wnt11 impedes MCTS attachment to ECM components and therefore can affect ovarian cancer progression.HIGHLIGHTSWnt11 reverse epithelial-mesenchymal transition in SKOV-3 cells.Wnt11-induced E- and N-cadherin decrease spheroid formation of SKOV-3 cells.Wnt11 inhibits disaggregation of spheroids via cadherins and integrin modulation.Wnt11 inhibits in vivo tumorigenesis and metastasis.Our findings shed light on the Wnt11 role in epithelial ovarian cancer.

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