Signals that regulate the oncogenic fate of neural stem cells and progenitors
2014 (English)In: Experimental Neurology, ISSN 0014-4886, E-ISSN 1090-2430, Vol. 260, 56-68 p.Article, review/survey (Refereed) Published
Brain tumors have frequently been associated with a neural stem cell (NSC) origin and contain stem-like tumor cells, so-called brain tumor stem cells (BTSCs) that share many features with normal NSCs. A stem cell state of BTSCs confers resistance to radiotherapy and treatment with alkylating agents. It is also a hallmark of aggressive brain tumors and is maintained by transcriptional networks that are also active in embryonic stem cells. Advances in reprogramming of somatic cells into induced pluripotent stem (iPS) cells have further identified genes that drive stemness. In this review, we will highlight the possible drivers of stemness in medulloblastoma and glioma, the most frequent types of primary malignant brain cancer in children and adults, respectively. Signals that drive expansion of developmentally defined neural precursor cells are also active in corresponding brain tumors. Transcriptomal subgroups of human medulloblastoma and glioma match features of NSCs but also more restricted progenitors. Lessons from genetically-engineered mouse (GEM) models show that temporally and regionally defined NSCs can give rise to distinct subgroups of medulloblastoma and glioma. We will further discuss how acquisition of stem cell features may drive brain tumorigenesis from a non-NSC origin. Genetic alterations, signaling pathways, and therapy-induced changes in the tumor microenvironment can drive reprogramming networks and induce stemness in brain tumors. Finally, we propose a model where dysregulation of microRNAs (miRNAs) that normally provide barriers against reprogramming plays an integral role in promoting stemness in brain tumors.
Place, publisher, year, edition, pages
2014. Vol. 260, 56-68 p.
Brain tumor, Progenitor, Neural stem cell, Glioma, Medulloblastoma, Reprogramming, miRNA
Cancer and Oncology Cell and Molecular Biology Neurosciences
Research subject Biology with specialization in Molecular Cell Biology; Pathology; Oncology
IdentifiersURN: urn:nbn:se:uu:diva-197463DOI: 10.1016/j.expneurol.2013.01.027ISI: 000341898000008OAI: oai:DiVA.org:uu-197463DiVA: diva2:613032
FunderSwedish Cancer Society, CAN 2010/899Swedish Research Council, K2012-99X-21953-01-3