Work

RBP2 induces stem-like cancer cells by promoting EMT and is a prognostic marker for renal cell carcinoma

Year: 2016

Type: article

Abstract: Renal cell carcinoma (RCC), one of the most common kidney cancers, has a poor prognosis. Epithelial to mesenchymal transition (EMT) is a hallmark of carcinoma invasion and metastasis. Several studies have examined the molecular regulation of EMT, but the relationship between histone demethylases and EMT is little understood. In this study, we investigated the role of retinoblastoma-binding protein-2 (RBP2), a histone demethylase that is highly expressed in RCC and is positively correlated with poor RCC prognosis in the regulation of EMT. We found that ectopic overexpression of RBP2 can induce cancer stem cell-like (CSC) phenotypes through EMT in RCC cells by converting them to a more mesenchymal phenotype. This results in increased resistance to apoptosis, which leads to enhanced tumor growth in xenograft models. Together, our data show that RBP2 is an epigenetic regulator that has an important role in the initiation of CSC phenotypes through EMT, leading to tumor progression. RBP2 is also a novel biomolecule for RCC diagnosis, and prognosis and may be a therapeutic target. A protein that shifts tumor cells into a more invasive state may serve as a marker for aggressive kidney cancers. Within many tumors, epithelial cells undergo physiological changes whereby they revert to a treatment-resistant, stem cell–like state that is capable of more aggressive growth. Researchers led by Shiying Xuan of the Ocean University of China, Qingdao, have found that a protein called RBP2 may promote this transition in certain kidney cancers. Forced RBP2 expression caused cultured renal cell carcinoma cells (RCC) to assume stem cell characteristics, suppressing cell death pathways that normally prevent uncontrolled growth. Elevated RBP2 in biopsies from RCC patients was also associated with worse prognosis, and triggered more aggressive growth of tumor cells transplanted into mice. These characteristics could make this protein a useful prognostic marker for this often deadly cancer.

Source: Experimental & Molecular Medicine

DOI: 10.1038/emm.2016.37