PMID- 17196391 OWN - NLM STAT- MEDLINE DCOM- 20070702 LR - 20220330 IS - 0960-9822 (Print) IS - 0960-9822 (Linking) VI - 17 IP - 2 DP - 2007 Jan 23 TI - HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. PG - 165-72 AB - Cancer stem cells are rare tumor cells characterized by their ability to self-renew and to induce tumorigenesis. They are present in gliomas and may be responsible for the lethality of these incurable brain tumors. In the most aggressive and invasive type, glioblastoma multiforme (GBM), an average of about one year spans the period between detection and death [1]. The resistence of gliomas to current therapies may be related to the existence of cancer stem cells [2-6]. We find that human gliomas display a stemness signature and demonstrate that HEDGEHOG (HH)-GLI signaling regulates the expression of stemness genes in and the self-renewal of CD133(+) glioma cancer stem cells. HH-GLI signaling is also required for sustained glioma growth and survival. It displays additive and synergistic effects with temozolomide (TMZ), the current chemotherapeutic agent of choice. TMZ, however, does not block glioma stem cell self-renewal. Finally, interference of HH-GLI signaling with cyclopamine or through lentiviral-mediated silencing demonstrates that the tumorigenicity of human gliomas in mice requires an active pathway. Our results reveal the essential role of HH-GLI signaling in controlling the behavior of human glioma cancer stem cells and offer new therapeutic possibilities. FAU - Clement, Virginie AU - Clement V AD - Department of Genetic Medicine and Development, University of Geneva Medical School, 8242 CMU, 1 rue Michel Servet, CH-1211 Geneva 4, Switzerland. FAU - Sanchez, Pilar AU - Sanchez P FAU - de Tribolet, Nicolas AU - de Tribolet N FAU - Radovanovic, Ivan AU - Radovanovic I FAU - Ruiz i Altaba, Ariel AU - Ruiz i Altaba A LA - eng GR - R01 NS037352-06/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20061228 PL - England TA - Curr Biol JT - Current biology : CB JID - 9107782 RN - 0 (GLI1 protein, human) RN - 0 (Hedgehog Proteins) RN - 0 (Transcription Factors) RN - 0 (Zinc Finger Protein GLI1) SB - IM EIN - Curr Biol. 2007 Jan 23;17(2):192 MH - Animals MH - Brain Neoplasms/*physiopathology MH - Gene Expression Regulation, Neoplastic MH - Glioma/*physiopathology MH - Hedgehog Proteins/*physiology MH - Humans MH - Mice MH - Neoplastic Stem Cells/*physiology MH - Signal Transduction/physiology MH - Transcription Factors/*physiology MH - Zinc Finger Protein GLI1 PMC - PMC1855204 MID - NIHMS16898 EDAT- 2007/01/02 09:00 MHDA- 2007/07/03 09:00 PMCR- 2007/04/24 CRDT- 2007/01/02 09:00 PHST- 2006/10/12 00:00 [received] PHST- 2006/11/09 00:00 [revised] PHST- 2006/11/13 00:00 [accepted] PHST- 2007/01/02 09:00 [pubmed] PHST- 2007/07/03 09:00 [medline] PHST- 2007/01/02 09:00 [entrez] PHST- 2007/04/24 00:00 [pmc-release] AID - S0960-9822(06)02514-0 [pii] AID - 10.1016/j.cub.2006.11.033 [doi] PST - ppublish SO - Curr Biol. 2007 Jan 23;17(2):165-72. doi: 10.1016/j.cub.2006.11.033. Epub 2006 Dec 28.