Endometrial cancer (EC) is the most common gynecological malignant tumor. The canonical Wnt/β-catenin signaling pathway plays a key role in regulating carcinogenesis, and the noncanonical Wnt5a-ROR1 pathway is an important regulator of Wnt signaling. However, the molecular mechanism by which ROR1 influences Wnt signaling in EC is not known. In this study, we found that ROR1 is expressed at higher levels in tumor tissues and blood samples from patients with stage II EC compared with patients with stage I disease. In vitro, human EC cell lines stably overexpressing ROR1 proliferated more rapidly and formed larger colonies than control cells. Consistent with this, overexpression or knockdown of ROR1 increased or decreased, respectively, the percentage of EC cells in M phase of the cell cycle. Elevated levels of ROR1 were associated with increased expression of Wnt5a and of cyclin D1 and c-Myc, two components of the Wnt signaling pathway. Finally, nude mice grew significantly larger tumors after subcutaneous injection of ROR1-overexpressing EC cells compared with control cells. These findings indicate a novel role for ROR1 in promoting EC cell proliferation by upregulating Wnt5a and stimulating the Wnt/β-catenin signaling pathway.
Keywords: ROR1; Wnt signaling pathway; Wnt5a; endometrial cancer; proliferation.
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