Human RAP2A Homolog of the Drosophila Asymmetric Cell Division Regulator Rap2l Targets the Stemness of Glioblastoma Stem Cells

Abstract

Asymmetric cell division (ACD) is a fundamental process to balance cell proliferation and differentiation during development and in the adult. Cancer stem cells (CSCs), a very small but highly malignant population within many human tumors, are able to provide differentiated progeny by ACD that contribute to the intratumoral heterogeneity, as well as to proliferate without control by symmetric, self-renewing divisions. Thus, ACD dysregulation in CSCs could trigger cancer progression. Here we consistently find low expression levels of RAP2A, the human homolog of the Drosophila ACD regulator Rap2l, in glioblastoma (GBM) patient samples, and observe that scarce levels of RAP2A are associated with poor clinical prognosis in GBM. Additionally, we show that restitution of RAP2A in GBM neurosphere cultures increases the ACD of glioblastoma stem cells (GSCs), decreasing their proliferation and expression of stem cell markers. Our results support that ACD failures in GSCs increases their spread, and that ACD amendment could contribute to reduce the expansion of GBM.