Hedgehog--Gli signaling in brain tumors: stem cells and paradevelopmental programs in cancer

Article Article scientifique Article Hedgehog--Gli signaling in brain tumors: stem cells and paradevelopmental programs in cancer eng 2004 author Ruiz Altaba Ariel 135639 author Stecca Barbara Ada 135752 author Sanchez Pilar 145-157 10.1016/S0304-3835(03)00451-8 15013214 0304-3835 The Hedgehog-Gli signaling pathway is involved in the regulation of the proliferation of precursors in different organs of the normal vertebrate embryo. These cells express Gli1 and may be the target of cancer-causing agents. Many tumor types derived from organs that contain Gli1+ precursors appear to consistently express Gli1, indicating their origin and/or the presence of an active pathway. Inappropriate pathway activation in a variety of precursor cells in model organisms leads to tumor formation while inhibition of the pathway in human tumor cells leads to a decrease in their proliferation. In the brain we have documented the expression of Gli1 in germinative zones, and a variety of brain tumors express GLI1, including medulloblastomas of the cerebellum and a number of gliomas of the cerebral cortex. The requirement for SHH-Gli signaling in the growth of the mouse brain, together with the ability of inappropriate pathway activation in the cerebellum to cause medulloblastomas, and the inhibition of the growth of a number of brain tumors with cyclopamine, a SHH signaling inhibitor, underscores the critical role of the SHH-GLI pathway in brain growth and tumor formation. Moreover, they highlight the components of this pathway as prime targets for drug development, with special emphasis on the GLI proteins. Such reagents would allow a rational therapeutic approach to highly intractable diseases. Brain/metabolism Brain Neoplasms/metabolism Hedgehog Proteins Humans Oncogene Proteins/metabolism Signal Transduction/physiology Stem Cells/physiology Trans-Activators/metabolism Transcription Factors/metabolism Zinc Finger Protein GLI1 true 446 Stemness dans le développement et les maladies: Signalisation, reprogrammation et mécanismes des métastases 776 Cancer Letters 204 2 48c9cf0f-8bc9-4c78-8612-214d1a000001 Article (Published version) Restricted PMID-15013214.pdf 332666 application/pdf restrictedAccess

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Hedgehog--Gli signaling in brain tumors: stem cells and paradevelopmental programs in cancer	Cancer Letters			2004	154	0

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Stecca, Barbara Ada