HumanRAP2AHomolog of theDrosophilaAsymmetric Cell Division RegulatorRap2lTargets the Stemness of Glioblastoma Stem Cells

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 ofRAP2A, the human homolog of theDrosophilaACD regulatorRap2l, in glioblastoma (GBM) patient samples, and observe that scarce levels ofRAP2Aare 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.