Sonic hedgehog inhibition reduces in vitro tumorigenesis and alters expression of GLI1-target genes in a desmoplastic medulloblastoma cell line

Medulloblastoma is one of the most frequent and aggressive tumors of childhood. The Sonic hedgehog (Shh) pathway, related to human development, is altered in most medulloblastomas: genes like Ptch, Smo, or Sufu suffer mutations in 15% to 25% of these tumors. We tested Shh inhibition in the Daoy medu...

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Authors: García-López, R. (Ricardo)|||/items/25e38308-23dc-4159-8914-a4ccc2fceb4a, Vera-Cano, B. (Beatriz)|||/items/77de971d-c2bd-4d48-a424-919216d9b55b, Vacas, A. (Andrés)|||/items/c76fdc2a-7197-45f6-9a7e-017bc9f2aedb, Rosa-Fernández-Pacheco, F.J. (Francisco Javier) de la|||/items/0330af5c-b62c-452f-bb9c-fab3c6c0db41, Gallo, G.O. (Gabriel Osvaldo)|||/items/75f283b7-fa24-4c88-902a-6fd5c8852f46, Alonso-Roldán, M.M. (Marta María)|||/items/b912e21e-f895-4efe-bc4c-de1ca8f36c37, Rey-Martinez, J.A. (Jorge Alberto)|||/items/4f0c1dfe-0655-4874-afa5-43702e38d4cc, Saez-Castresana, J. (Javier)|||/items/52f31ab0-8555-470d-af21-e677a1b3eff8
Format: article
Publication Date:2013
Country:España
Institution:Universidad de Navarra
Repository:Dadun. Depósito Académico Digital de la Universidad de Navarra
Language:English
OAI Identifier:oai:dadun.unav.edu:10171/64527
Online Access:https://hdl.handle.net/10171/64527
Access Level:Open access
Keyword:Sonic hedgehog
Cyclopamine
siRNA
Gli1, Ptch
Smo
In vitro tumorigenesis
Medulloblastoma
Description
Summary:Medulloblastoma is one of the most frequent and aggressive tumors of childhood. The Sonic hedgehog (Shh) pathway, related to human development, is altered in most medulloblastomas: genes like Ptch, Smo, or Sufu suffer mutations in 15% to 25% of these tumors. We tested Shh inhibition in the Daoy medulloblastoma cell line by two methods: a molecular one, direct Gli1 siRNA inhibition; and a pharmacological inhibition of Smo, upstream of Gli1, by cyclopamine. Afterwards, a comparison of cellular and molecular responses was done. In general, we proved that cell viability, cell migration and cell colony formation decreased after Shh inhibition, which might confer a less tumorigenic status to Daoy cells. Moreover, we assessed the expression of different Gli1 target genes and other genes and found that Shh shows a crosstalk with oncogenes and tumor suppressor genes that have been described in numerous tumors. All these experiments give an overview of the Shh pathway in medulloblastoma, together with the demonstration of the efficacy of cyclopamine and Gli1 siRNA Shh inhibition in vitro.

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