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WNT11/ROR2 signaling is associated with tumor invasion and poor survival in breast cancer [patients]

ABSTRACT: Breast cancer is the most common cancer in women with more than two million new cases diagnosed in 2018. Patients frequently develop metastases in the course of their disease which limit survival due to the lack of a curative treatment. One signaling pathway that is frequently involved in cancer initiation and progression is the WNT pathway. Breast cancer has been associated with activation of the WNT signaling pathway, although the underlying molecular mechanisms are still unclear. Here, we found the WNT receptor ROR2 to be highly expressed in aggressive breast tumors and associated with worse metastasis-free survival. In this study we addressed this question and demonstrated for the first time that WNT11 is a novel ligand for ROR2 in humans. WNT11 binds to the CRD of ROR2 and mediates WNT/PCP signaling via the RHO/ROCK pathway that confers an aggressive phenotype to breast cancer cells. ROR2 and WNT11 are both highly expressed in human brain metastases and linked with short patient survival.

ORGANISM(S): Homo sapiens

PROVIDER: GSE161865 | GEO | 2022/02/21

REPOSITORIES: GEO

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WNT11/ROR2 signaling is associated with tumor invasion and poor survival in breast cancer

Project description:Breast cancer has been associated with activation of the WNT signaling pathway, although the underlying molecular mechanisms are still unclear. In order to understand the molecular basis of these observations, we overexpressed ROR2 in human breast cancer cell lines and characterized them by RNA-Sequencing. High levels of ROR2 were associated with defects in cell morphology and cell-cell-contacts leading to increased tumor invasiveness. Using gene expression analysis we demonstrated an upregulation of several non-canonical WNT ligands in ROR2-overexpressing breast cancer cells, in particular WNT11. Knockdown of WNT11 reversed the pro-invasive phenotype and the cellular changes in ROR2-overexpressing cells. Taken together, our studies revealed a novel auto-stimulatory loop in which ROR2 triggers the expression of its own ligands, e.g. WNT11, resulting in enhanced tumor invasion associated with breast cancer metastasis.

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WNT11/ROR2 signaling is associated with tumor invasion and poor survival in breast cancer

Project description:WNT11/ROR2 signaling is associated with tumor invasion and poor survival in breast cancer

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WNT11 is a novel ligand for ROR2 in human breast cancer

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WNT11/ROR2 signaling is associated with tumor invasion and poor survival in breast cancer [patients]

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Genome wide screen reveals WNT11, a noncanonical WNT gene, as a target of ETS transcription factor ERG

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