Distinct cellular origin and genetic requirement of Hedgehog-Gli in postnatal rhabdomyosarcoma genesis
Authors
Rajurkar, Mihir S.Huang, He
Cotton, Jennifer L.
Brooks, Julie K.
Sicklick, J.
McMahon, A. P.
Mao, Junhao
UMass Chan Affiliations
Department of Cancer BiologyDocument Type
Journal ArticlePublication Date
2014-11-13Keywords
AnimalsCell Lineage
Cells, Cultured
Gene Expression Regulation, Neoplastic
Hedgehog Proteins
Humans
Immunoblotting
Kruppel-Like Transcription Factors
Mice, 129 Strain
Mice, Knockout
Nerve Tissue Proteins
PAX7 Transcription Factor
RNA Interference
Receptors, G-Protein-Coupled
Reverse Transcriptase Polymerase Chain Reaction
Rhabdomyosarcoma
SOXC Transcription Factors
Satellite Cells, Skeletal Muscle
Tumor Cells, Cultured
Hedgehog
Gli
progenitor
rhbdomyosarcoma
Cancer Biology
Cell Biology
Neoplasms
Metadata
Show full item recordAbstract
Dysregulation of the Hedgehog (Hh)-Gli signaling pathway is implicated in a variety of human cancers, including basal cell carcinoma (BCC), medulloblastoma (MB) and embryonal rhabdhomyosarcoma (eRMS), three principle tumors associated with human Gorlin syndrome. However, the cells of origin of these tumors, including eRMS, remain poorly understood. In this study, we explore the cell populations that give rise to Hh-related tumors by specifically activating Smoothened (Smo) in both Hh-producing and -responsive cell lineages in postnatal mice. Interestingly, we find that unlike BCC and MB, eRMS originates from the stem/progenitor populations that do not normally receive active Hh signaling. Furthermore, we find that the myogenic lineage in postnatal mice is largely Hh quiescent and that Pax7-expressing muscle satellite cells are not able to give rise to eRMS upon Smo or Gli1/2 overactivation in vivo, suggesting that Hh-induced skeletal muscle eRMS arises from Hh/Gli quiescent non-myogenic cells. In addition, using the Gli1 null allele and a Gli3 repressor allele, we reveal a specific genetic requirement for Gli proteins in Hh-induced eRMS formation and provide molecular evidence for the involvement of Sox4/11 in eRMS cell survival and differentiation.Source
Oncogene. 2014 Nov 13;33(46):5370-8. doi: 10.1038/onc.2013.480. Link to article on publisher's site.DOI
10.1038/onc.2013.480Permanent Link to this Item
http://hdl.handle.net/20.500.14038/30516PubMed ID
24276242Notes
Article title in PubMed Central varies from published article title.
Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/onc.2013.480