English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Hedgehog/Patched-associated rhabdomyosarcoma formation from delta1-expressing mesodermal cells

Nitzki, F., Cuvelier, N., Draeger, J., Schneider, A., Braun, T., & Hahn, H. (2016). Hedgehog/Patched-associated rhabdomyosarcoma formation from delta1-expressing mesodermal cells. ONCOGENE, 35(22), 2923-2931. doi:10.1038/onc.2015.346.

Item is

Basic

show hide
Genre: Journal Article

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Nitzki, F., Author
Cuvelier, N., Author
Draeger, J., Author
Schneider, André1, Author              
Braun, Thomas1, Author              
Hahn, H., Author
Affiliations:
1Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591698              

Content

show
hide
Free keywords: SKELETAL-MUSCLE DEVELOPMENT; WNT INHIBITORY FACTOR-1; EMBRYONAL RHABDOMYOSARCOMA; ALVEOLAR RHABDOMYOSARCOMA; MOUSE MODEL; STEM-CELL; GENE; MICE; EXPRESSION; MYOGENESISBiochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity;
 Abstract: Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. In children, the 2 major RMS subtypes are alveolar and embryonal RMS. Aberrant Hedgehog/Patched1 (Hh/Ptch) signaling is a hallmark of embryonal RMS. We demonstrate that mice carrying a Ptch mutation in mesodermal Delta1-expressing cells develop embryonal-like RMS at a similar rate as mice harboring a Ptch mutation in the germline or the brachury-expressing mesoderm. The tumor incidence decreases dramatically when Ptch is mutated in Myf5- or Pax3-expressing cells. No RMS develop from Myogenin/Mef2c-expressing cells. This suggests that Hh/Ptch-associated RMS are derived from Delta1-positive, Myf5-negative, Myogenin-negative and Pax3-negative mesodermal progenitors that can undergo myogenic differentiation but lack stable lineage commitment. Additional preliminary genetic data and data on mesodermal progenitors further imply an interplay of Hh/Ptch and Delta/Notch signaling activity during RMS initiation. In contrast, Wnt signals supposedly suppress RMS formation because RMS multiplicity decreases after inactivation of the Wnt-inhibitor Wif1. Finally, our results strongly suggest that the tumor-initiating event determines the lineage of RMS origin.

Details

show
hide
Language(s): eng - English
 Dates: 2016
 Publication Status: Published in print
 Pages: 9
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000377473700012
DOI: 10.1038/onc.2015.346
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: ONCOGENE
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND : NATURE PUBLISHING GROUP
Pages: - Volume / Issue: 35 (22) Sequence Number: - Start / End Page: 2923 - 2931 Identifier: ISSN: 0950-9232