Medulloblastoma can be Initiated by Deletion of patched in Lineage-Restricted Progenitors or Stem Cells
By Zeng-jie Yang, Tammy Ellis, S. Markant, T. Read, J. Kessler, M. Bourboulas, U. Schüller, R. Machold, G. Fishell, D. Rowitch and 2 more. Cancer Cell, 2008
683 citations recorded by the source corpus.
SUMMARY Medulloblastoma is the most common malignant brain tumor in children, but the cells from which it arises remain unclear. Here we examine the origin of medulloblastoma resulting from mutations in the Sonic hedgehog (Shh) pathway. We show that activation of Shh signaling in neuronal progenitors causes medulloblastoma by 3 months of age. Shh pathway activation in stem cells promotes stem cell proliferation, but only causes tumors after commitment to – and expansion of – the neuronal lineage. Notably, tumors initiated in stem cells develop more rapidly than those initiated in progenitors, with all animals succumbing by 3–4 weeks. These studies suggest that medulloblastoma can be initiated in progenitors or stem cells, but that Shh-induced tumorigenesis is associated with neuronal lineage commitment.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/c4466243fcdf1fd1166e6a6f840a90c1bf6acc3e
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Citations in the corpus
- Cells of origin in cancer (2011, background): “Constitutive hedgehog signalling (due to loss of Ptc or activation of Smo ) in either the stem-cell compartment or granule neuron progenitor cells could initiate medulloblastomas but not astrocytomas or oligodendroglioma”
- Cancer Stem Cells (CSCs) in Drug Resistance and their Therapeutic Implications in Cancer Treatment (2018, background): “In addition, it has been shown that oncogenic Hh signaling can promote medulloblastoma from either lineage-restricted granule cell progenitors or stem cells [48, 49].”
- Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Hedgehog-induced medulloblastoma (2008, neutral): “We next investigated expression of the bHLH protein Olig2, which marks multilineage progenitor populations of the forebrain and the spinal cord (Petryniak et al., 2007; Lu et al., 2002; Zhou and Anderson, 2002).”
- Cancer stem cells: impact, heterogeneity, and uncertainty. (2012, background): “Medulloblastomas can arise either from Sonic Hedgehog pathway activation in granule neuron precursors of the cerebellum or from Wnt pathway activation in dorsal brainstem progenitors (Gibson et al., 2010; Schüller et al., 2008; Yang et al., 2008) (Figure 2B).”
- Targeting brain cancer: advances in the molecular pathology of malignant glioma and medulloblastoma (2010, background): “Mouse modelling has further demonstrated the sufficiency of SHH signalling to generate medulloblastomas in multiple cell types in the developing hindbrain (discussed below”
- Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas (2012, background): “Most likely, they will also have different cellular origins, as has already been shown for the WNT and SHH subgroups [7, 8, 23, 26].”
- Tumour-initiating cells: challenges and opportunities for anticancer drug discovery (2009, background): “, whereas tumour-initiating cells from many solid tumours could be proliferativ”