In Cancer Research this week, a French research team report that the protein ZNF217 is a marker of poor prognosis in breast cancer and drives epithelial-to-mesenchymal transition and invasion. The team analyzed ZNF217 expression in breast cancer cells lines and mouse models and found that high expression levels are associated with poor prognosis and the development of metastases. "Overexpression of ZNF217 in breast cancer cells stimulated migration and invasion in vitro and promoted the development of spontaneous lung or node metastases in mice in vivo," the team writes. The protein also prompts EMT in human mammary epithelial cells through the TGF-β-activated Smad signaling pathway. "Inhibition of the TGF-β pathway led to the reversal of ZNF217-mediated EMT," the team adds. "Together, our findings indicate that ZNF217 mRNA expression may represent a novel prognostic biomarker in breast cancer."
Also in Cancer Research this week, National Cancer Institute investigators report that perturbations in Rb, p53, and BRCA1 or BRCA2 can act together to induce the development of metastatic serous epithelial ovarian cancer. Using genetically engineered mice, the reseachers analyzed the roles of multiple pathway perturbations in the initiation and progression of epithelial ovarian cancer. They found that the inactivation of RB-mediated tumor suppression induced proliferation with progression to stage I cancer and that additional p53 mutations, both in the presence and absence of BRCA mutations, caused progression of the disease. "As in human [serous epithelial ovarian cancer], mice developed peritoneal carcinomatosis, ascites, and distant metastases," the authors write. "Unbiased gene expression and metabolomic profiling confirmed that Rb, p53, and Brca1/2-triple mutant tumors aligned with human SEOC, and not with other intraperitoneal cancers."
Finally in Cancer Research this week, a team of researchers in the US and South Korea report that MET signaling regulates glioblastoma stem cells. The team studied human primary glioblastoma samples and identified a distinct population of cells expressing a high level of MET. The samples were found to be "highly clonogenic, tumorigenic, and resistant to radiation," the team writes, adding that inhibition of MET signaling in stem cells disrupted tumor growth and invasiveness both in vitro and in vivo. "Together, our findings indicate that MET activation in GBM is a functional requisite for the cancer stem cell phenotype and a promising therapeutic target," it adds.