Effects of Notch signalling on the expression of SEMA3C, HMGA2, CXCL14, CXCR7, and CCL20 in breast cancer
Effects of Notch signalling on the expression of SEMA3C, HMGA2, CXCL14, CXCR7, and CCL20 in breast cancer
Metastasis is the main reason for death in breast cancer. Understanding the molecular players in metastasis is crucial fordiagnostic and therapeutic purposes. Notch signalling plays an oncogenic role in breast tumorigenesis and is involved in metastasis.Downstream mediators of Notch signalling in prometastatic processes are not yet fully discovered. Here we aimed to investigate whetherNotch signalling regulates the expression of SEMA3C, HMGA2, CXCL14, CXCR7, and CCL20, which are involved in prometastaticprocesses, in breast cell lines. To this end, expression of the selected genes was analysed following Notch activation by overexpression ofthe Notch1 intracellular domain in the normal breast epithelial cell line MCF10A, and inhibition by silencing of the Notch transcriptionalmediator RBPjκ in the breast cancer cell line MDA MB 231. SEMA3C and HMGA2 mRNA were decreased, while CXCL14 and CXCR7mRNA were increased significantly in response to Notch activation in MCF10A cells. Notch inhibition in MDA MB 231 cells significantlydecreased HMGA2 and CCL20 mRNA. Protein levels were not significantly altered by Notch modulation. In conclusion, we showed thatNotch signalling regulates expression of SEMA3C, CXCL14, CCL20, CXCR7, and HMGA2, which are prominent candidate genes thatmight function downstream of Notch to induce prometastatic processes.
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