Human <i>RAP2A</i> homolog of the <i>Drosophila</i> asymmetric cell division regulator <i>Rap2l</i> 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 <i>RAP2A</i>, the human homolog of the <i>Drosophila</i> ACD regulator <i>Rap2l</i>, in glioblastoma (GBM) patient samples, and observe that scarce levels of <i>RAP2A</i> 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 increase their spread and ACD amendment could contribute to reduce the expansion of GBM.