From: Subject: HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal and tumorigenicity Date: Thu, 21 Feb 2008 17:23:33 +0100 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0000_01C874AE.7C051AE0" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.3198 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01C874AE.7C051AE0 Content-Type: text/html; charset="utf-8" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1855204&rendertype=abstract =EF=BB=BF HEDGEHOG-GLI1 signaling regulates human glioma = growth, cancer stem cell self-renewal and tumorigenicity
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PubMed=20 articles by:
Clement, V. 
Sanchez, P. 
de Tribolet, N. 
Altaba, = A. 
Curr Biol. Author manuscript; = available in=20 PMC 2007 April 24.
Published in final edited form = as:
Curr = Biol.=20 2007 January = 23;=20 17(2):=20 165=E2=80=93172.
Published=20 online 2006 December 28. doi:=20 10.1016/j.cub.2006.11.033.
Copyright = notice and Disclaimer=
HEDGEHOG-GLI1 signaling regulates human = glioma growth,=20 cancer stem cell self-renewal and tumorigenicity
Virginie = Clement,1 Pilar=20 Sanchez,1,2 Nicolas de Tribolet,3 = Ivan=20 Radovanovic,3 and Ariel Ruiz i Altaba1
1 Department of Genetic Medicine = and=20 Development, University of Geneva Medical School, 8242 CMU, 1 rue = Michel=20 Servet, CH-1211 Geneva 4, Switzerland
3 Department of Neurosurgery, = Geneva=20 Cantonal Hospital, CH-1211 Geneva 4, Switzerland
Correspondence: Email: Ariel.RuizAltaba/at/medecine.unige.ch (ARA)
2Present address: = Departament de=20 Biologia Cel.lular, Universitat de Val=C3=A8ncia, 46100 Burjassot, = Val=C3=A8ncia,=20 Spain.
3D"Small=20 The publisher's final edited version of this article is available = at Curr Biol.
3D"Small=20 This article has been corrected. See the = correction in=20 volume 17 on page 192.
3D"Small=20 See other articles in PMC that cite=20 the published article.
 
Summary
Cancer stem = cells are rare=20 tumor cells characterized by their ability to self-renew and to = induce=20 tumorigenesis. They are present in gliomas and may be responsible = for the=20 lethality of these incurable brain tumors. In the most aggressive = and=20 invasive type, glioblastoma multiforme (GBM), an average of = =C2=B11 year spans=20 the period between detection and death (1). The resistence of = gliomas to=20 current therapies may be related to the existence of cancer stem = cells=20 (2=E2=80=936). We find that human gliomas display a stemness = signature and=20 demonstrate that HEDGEHOG (HH)-GLI signaling regulates the = expression of=20 stemness genes in and the self-renewal of CD133+ glioma cancer = stem cells.=20 HH-GLI signaling is also required for sustained glioma growth and=20 survival, displaying additive and synergistic effects with = temozolomide,=20 the current chemotherapeutic agent of choice, which does not = affect glioma=20 stem cell self-renewal. Finally, interference of HH-GLI signaling = with=20 cyclopamine or through lentiviral-mediated silencing demonstrates = that the=20 tumorigenicity of human gliomas in nude mice requires an active = pathway.=20 Our results reveal the essential role of HH-GLI signaling in = controlling=20 the behavior of human glioma cancer stem cells and offer new = therapeutic=20 possibilities.
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-37px -57px; CURSOR: default } .scale-pmc A.scale-2 { BACKGROUND-POSITION: 3px -77px } .scale-pmc A.scale-2:hover { BACKGROUND-POSITION: -77px -77px } .scale-pmc A.selected-2 { BACKGROUND-POSITION: -37px -77px; CURSOR: default } .scale-pmc A.selected-2:hover { BACKGROUND-POSITION: -37px -77px; CURSOR: default } .scale-pmc A.scale-3 { BACKGROUND-POSITION: 3px -97px } .scale-pmc A.scale-3:hover { BACKGROUND-POSITION: -77px -97px } .scale-pmc A.selected-3 { BACKGROUND-POSITION: -37px -97px; CURSOR: default } .scale-pmc A.selected-3:hover { BACKGROUND-POSITION: -37px -97px; CURSOR: default } .scale-pmc A.scale-4 { BACKGROUND-POSITION: 3px -117px } .scale-pmc A.scale-4:hover { BACKGROUND-POSITION: -77px -117px } .scale-pmc A.selected-4 { BACKGROUND-POSITION: -37px -117px; CURSOR: default } .scale-pmc A.selected-4:hover { BACKGROUND-POSITION: -37px -117px; CURSOR: default } .scale-pmc A.scale-5 { BACKGROUND-POSITION: 3px -137px } .scale-pmc A.scale-5:hover { BACKGROUND-POSITION: -77px -137px } .scale-pmc A.selected-5 { BACKGROUND-POSITION: -37px -137px; CURSOR: default } .scale-pmc A.selected-5:hover { BACKGROUND-POSITION: -37px -137px; CURSOR: default } .scale-pmc A.scale-6 { BACKGROUND-POSITION: 3px -157px } .scale-pmc A.scale-6:hover { BACKGROUND-POSITION: -77px -157px } .scale-pmc A.selected-6 { BACKGROUND-POSITION: -37px -157px; CURSOR: default } .scale-pmc A.selected-6:hover { BACKGROUND-POSITION: -37px -157px; CURSOR: default } .scale-pmc A.scale-7 { BACKGROUND-POSITION: 3px -177px } .scale-pmc A.scale-7:hover { BACKGROUND-POSITION: -77px -177px } .scale-pmc A.selected-7 { BACKGROUND-POSITION: -37px -177px; CURSOR: default } .scale-pmc A.selected-7:hover { BACKGROUND-POSITION: -37px -177px; CURSOR: default } .scale-pmc A.scale-8 { BACKGROUND-POSITION: 3px -207px } .scale-pmc A.scale-8:hover { BACKGROUND-POSITION: -77px -207px } .scale-pmc A.selected-8 { BACKGROUND-POSITION: -37px -207px; CURSOR: default } .scale-pmc A.selected-8:hover { BACKGROUND-POSITION: -37px -207px; CURSOR: default } ------=_NextPart_000_0000_01C874AE.7C051AE0 Content-Type: application/octet-stream Content-Transfer-Encoding: quoted-printable Content-Location: http://www.pubmedcentral.nih.gov/corehtml/pmc/js/common.js // Called from many places to handle links.=0A= // Params:=0A= // link: URL. 'this' to reuse same window, else ""=0A= // windowname: Reference name for window=0A= // additional: Attributes for window.open, from:=0A= // width, height, resizable, scrollbars, toolbar, location, = directories,=0A= // status, menubar, copyhistory.=0A= // Notes: Book version always provides menubar, toolbar, etc.=0A= //=0A= function startTargetBook(link,windowname,width,height,additional) =0A= {=0A= if(! window.focus)=0A= return;=0A= var sizestring =3D ",width=3D" + width + ",height=3D" + height;=0A= var opt =3D = "menubar=3Dyes,toolbar=3Dyes,status=3Dyes,scrollbars,resizable,dependent=3D= yes";=0A= var allOptions =3D opt + sizestring;=0A= if (additional) { allOptions =3D allOptions + additional; }=0A= //alert("In startTargetBook, additional: " + additional);=0A= =0A= w =3D window.open("",windowname, allOptions);=0A= w.focus();=0A= link.target=3Dwindowname;=0A= }=0A= =0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function startTarget(link,windowname,width,height) =0A= {=0A= if(! window.focus)=0A= return;=0A= var sizestring =3D ",width=3D" + width + ",height=3D" + height;=0A= w =3D = window.open("",windowname,"scrollbars,resizable,dependent=3Dyes" + = sizestring);=0A= w.focus();=0A= link.target=3Dwindowname;=0A= }=0A= =0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function focuswin(windowname) =0A= {=0A= w =3D = window.open("",windowname,"menubar=3Dyes,scrollbars=3Dyes,toolbar=3Dyes,l= ocation=3Dyes,status=3Dyes,directories=3Dyes,resizable=3Dyes");=0A= w.focus();=0A= return true;=0A= }=0A= =0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function reverseString (inStr)=0A= {=0A= var outStr =3D ''=0A= =0A= for (i =3D0; i <=3D inStr.length; i++)=0A= {=0A= outStr =3D inStr.charAt(i) + outStr=0A= }=0A= =0A= return outStr=0A= }=0A= =0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function reverseAndReplaceString (inStr, findStr, newStr)=0A= {=0A= return reverseString(inStr).replace(findStr, newStr)=0A= }=0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function initUnObscureEmail (className, innerHTML)=0A= {=0A= =0A= try{=0A= if (window.addEventListener)=0A= window.addEventListener('load', function() {unObscureEmail = (className, innerHTML)}, false)=0A= else if (window.attachEvent)=0A= window.attachEvent('onload', function() {unObscureEmail = (className, innerHTML)})=0A= }catch(e){=0A= }=0A= }=0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function unObscureEmail (className, innerHTML)=0A= {=0A= try {=0A= if (typeof(unObscuredEmails) =3D=3D 'undefined')=0A= unObscuredEmails =3D new Array()=0A= =0A= if (! unObscuredEmails[className])=0A= {=0A= =0A= var elmnts =3D document.getElementsByTagName("span")=0A= for (var i =3D 0, len =3D elmnts.length; i < len; i++)=0A= {=0A= if (elmnts.item(i).className.indexOf(className, " ") = !=3D -1)=0A= {=0A= elmnts.item(i).innerHTML =3D innerHTML;=0A= unObscuredEmails[className] =3D true=0A= =0A= }=0A= }=0A= }=0A= }=0A= catch(e){=0A= }=0A= }=0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function pubMedDbLinkSubmit(control) {=0A= try{=0A= if (control.pubmedOption) =0A= control =3D control.pubmedOption=0A= if (control.options)=0A= location.href =3D = control.options[control.options.selectedIndex].value;=0A= }=0A= catch(e){}=0A= return false;=0A= }=0A= ------=_NextPart_000_0000_01C874AE.7C051AE0 Content-Type: application/octet-stream Content-Transfer-Encoding: quoted-printable Content-Location: http://www.ncbi.nlm.nih.gov/corehtml/jsutils/utils.1.js // $Id: utils.1.js,v 1.12 2008/01/14 14:44:06 sponomar Exp $=0A= var utils=3D{=0A= KeyCode_TAB:9,=0A= KeyCode_DELETE:46,=0A= KeyCode_BACKSPACE:8,=0A= KeyCode_LEFT_ARROW:37,=0A= KeyCode_RIGHT_ARROW:39,=0A= KeyCode_HOME:36,=0A= KeyCode_END:35,=0A= KeyCode_PAGE_UP:33,=0A= KeyCode_PAGE_DOWN:34,=0A= KeyCode_UP_ARROW:38,=0A= KeyCode_DOWN_ARROW:40,=0A= KeyCode_ESC:27,=0A= KeyCode_ENTER:13,=0A= KeyCode_SPACE:32,=0A= KeyCode_SHIFT_KEY:16,=0A= KeyCode_CTRL_KEY:17,=0A= KeyCode_ALT_KEY:18,=0A= KeyCode_LEFT_MS_WINDOWS_KEY:91,=0A= KeyCode_RIGHT_MS_WINDOWS_KEY:92,=0A= KeyCode_MS_MENU_KEY:93,=0A= isObject: function(a) { return (a && typeof a =3D=3D 'object'); 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