Activating Smoothened mutations in sporadic basal-cell carcinoma

Nature
J XieFrederic J de Sauvage

Abstract

Basal-cell carcinomas (BCCs) are the commonest human cancer. Insight into their genesis came from identification of mutations in the PATCHED gene (PTCH) in patients with the basal-cell nevus syndrome, a hereditary disease characterized by multiple BCCs and by developmental abnormalities. The binding of Sonic hedgehog (SHH) to its receptor, PTCH, is thought to prevent normal inhibition by PTCH of Smoothened (SMO), a seven-span transmembrane protein. According to this model, the inhibition of SMO signalling is relieved following mutational inactivation of PTCH in basal-cell nevus syndrome. We report here the identification of activating somatic missense mutations in the SMO gene itself in sporadic BCCs from three patients. Mutant SMO, unlike wild type, can cooperate with adenovirus E1A to transform rat embryonic fibroblast cells in culture. Furthermore, skin abnormalities similar to BCCs developed in transgenic murine skin overexpressing mutant SMO. These findings support the role of SMO as a signalling component of the SHH-receptor complex and provide direct evidence that mutated SMO can function as an oncogene in BCCs.

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Jun 1, 2014·Archives of Pathology & Laboratory Medicine·Stefan Kraft, Scott R Granter
Sep 19, 2014·World Journal of Clinical Cases·Vivian T YinBita Esmaeli
Oct 12, 2007·Physiological Reviews·Gijs R van den Brink
Aug 28, 2019·Angewandte Chemie·Lea KremerHerbert Waldmann
Oct 15, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Florian HermsNicole Basset-Seguin
Jan 26, 2020·International Journal of Molecular Sciences·Barbara BelleiLaura Eibenschutz
Feb 22, 2020·Wiley Interdisciplinary Reviews. Developmental Biology·Eduardo D Gigante, Tamara Caspary
Mar 1, 2020·Journal of Applied Toxicology : JAT·Peter C W LuLouise M Winn
Jun 3, 2000·The Journal of Biological Chemistry·D L DeCampM R Lerner
Oct 18, 2000·The Journal of Biological Chemistry·X Q Wang, J A Rothnagel
May 29, 2000·The Journal of Biological Chemistry·M A StegmanDavid J Robbins
Apr 20, 2002·The Journal of Biological Chemistry·Robert A McCarthyW Scott Argraves
Jun 20, 2002·The Journal of Biological Chemistry·Evans C BaileyRonald L Johnson
Nov 15, 2019·The American Journal of Surgical Pathology·Ivan J StojanovLynette M Sholl
Oct 14, 2003·The Journal of Biological Chemistry·Rebecca L H BigelowTimothy J McDonnell
Jun 17, 2014·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Clarissa Araújo Silva GurgelEduardo Antônio Gonçalves Ramos
Jun 14, 2014·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Michal Reichman-Fried, Erez Raz
Mar 19, 2016·Molecular Cancer·Ann Hanna, Lalita A Shevde
Mar 24, 2009·The Journal of Pharmacology and Experimental Therapeutics·Cynthia M RomingerDavid H Rominger
Sep 2, 2011·Molecular Carcinogenesis·Karin Heby-HenricsonStephan Teglund
May 6, 2020·Head & Neck·Ulrich MoserDietmar Thurnher
Nov 10, 2015·International Journal of Oncology·Yoshinobu SaitohSetsuro Komiya
Mar 2, 2016·Theoretical Biology & Medical Modelling·Nicolas CarelsJack Adam Tuszynski
Apr 22, 2010·Experimental Biology and Medicine·Maarten F Bijlsma, C Arnold Spek
May 30, 2012·Seminars in Cutaneous Medicine and Surgery·Kim ChongUCSF High Risk Skin Cancer Program
Nov 25, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Mehdi H ShahiJavier S Castresana
Dec 19, 2014·The Journal of Biological Chemistry·Jacqueline M McCabe, Daniel J Leahy
Jul 2, 2015·The Journal of Biological Chemistry·Benedikt LinderAnja Uhmann
Nov 23, 2015·Archives of Dermatological Research·Aleksandra LesiakJoanna Narbutt
Sep 28, 2017·Anais Brasileiros De Dermatologia·Erik Montagna, Otávio Sérgio Lopes
Sep 2, 2018·Disease Models & Mechanisms·Joseph Burclaff, Jason C Mills
Feb 2, 2019·The Journal of Clinical Investigation·David R Raleigh, Jeremy F Reiter
Jun 28, 2019·Targeted Oncology·Ralf Gutzmer, James A Solomon
Aug 28, 2019·Journal of the American Society of Nephrology : JASN·Ming MaKarel F Liem
Nov 29, 2019·Cell Communication and Signaling : CCS·Yan XuJaffer A Ajani
Sep 25, 2019·Annals of Surgical Oncology·Ann Y Lee, Russell S Berman
Jan 28, 2005·Journal of Neuro-oncology·Torsten PietschJames T Rutka
Jul 27, 2006·The Journal of Biological Chemistry·Matthieu De RivoyreIsabelle Mus-Veteau
Feb 23, 2012·Arthritis and Rheumatism·Angelika HornJörg H W Distler
Sep 16, 2015·Applied Immunohistochemistry & Molecular Morphology : AIMM·Rosane Borges DiasClarissa Araújo Gurgel Rocha
Mar 15, 2016·Frontiers in Biology·Kai Jiang, Jianhang Jia
Nov 23, 2017·Frontiers in Endocrinology·Xiulong XuRichard A Prinz
Apr 18, 2017·Expert Opinion on Pharmacotherapy·Teresa Amaral, Claus Garbe
Jun 6, 2018·Cellular Oncology (Dordrecht)·Veronique L VeenstraMaarten F Bijlsma
Aug 26, 2018·International Journal of Molecular Sciences·Stephanie HehlgansShahram Ghanaati
Apr 5, 2018·Journal of Developmental Biology·Yoshinori Abe, Nobuyuki Tanaka
Jul 30, 2019·Frontiers in Medicine·Keiji TaneseTakeru Funakoshi
May 22, 2020·The Journal of Cell Biology·Paurav B DesaiG J Pazour
Aug 3, 2011·Genesis : the Journal of Genetics and Development·Fernando F MigoneSusan M Quirk
May 23, 2014·Science China. Life Sciences·Chen Zhao
May 18, 2013·International Journal of Dermatology·Lucinda S Liu, Oscar R Colegio
Jun 27, 2015·Cancer Chemotherapy and Pharmacology·Juan WangWenfu Tan
Jun 18, 2011·Cancer Science·Hideya Onishi, Mitsuo Katano
Feb 20, 2015·Annals of Plastic Surgery·Jessica A ChingMichael A Harrington
Mar 30, 2017·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Huifa MaXiangyang Yu
Sep 12, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Matthew W TurnerOwen M McDougal
Aug 23, 2019·Acta chirurgica Belgica·Jos VellemanJan J Vranckx
Jan 2, 2019·Proceedings of the National Academy of Sciences of the United States of America·Boyan ZhangChuanmao Zhang
Jul 3, 2020·Frontiers in Chemistry·Taikangxiang YunYing Liu
Sep 23, 2020·Cells·Daniel DohenyHui-Wen Lo
Mar 6, 2008·The Journal of Biological Chemistry·Thomas EichbergerAnna-Maria Frischauf
Oct 10, 2015·The Journal of Biological Chemistry·Jaskirat SinghSuzie J Scales
Apr 18, 2015·Hormones : International Journal of Endocrinology and Metabolism·Maria P YavropoulouJohn G Yovos
Feb 15, 2011·Oncotarget·Joshua C Curtin, Matthew V Lorenzi
Mar 16, 2013·The British Journal of Dermatology·F R Ali, J T Lear
Oct 13, 2012·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Pamela V TranRolf W Stottmann
Jul 2, 2017·The Journal of Biological Chemistry·Justine M PinskeyBenjamin L Allen
Dec 13, 2018·Pathology Oncology Research : POR·Madiha NiyazSyed Mudassar
Nov 11, 2018·Development·Philip W Ingham
Mar 17, 2015·Proceedings of the National Academy of Sciences of the United States of America·Eun Jin SonJinwoong Bok
Jul 8, 2008·Acta Biochimica Et Biophysica Sinica·Jingwu Xie
Mar 20, 2019·International Journal of Molecular Sciences·Lucilla FabbriNathalie M Mazure
Apr 18, 2019·Cancers·Elisabeth PeerFritz Aberger
Jan 29, 2020·Scientific Reports·Amir SternfeldNitza Goldenberg-Cohen
Jan 31, 2020·Dermatology and Therapy·Abrar ChoudhuryUrsula E Lang
Jan 13, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Guangjun JiaoKang Yang
Nov 30, 2019·Frontiers in Genetics·Noriaki SasaiToru Kondo
Nov 22, 2020·Pharmacological Reviews·Torsten Schöneberg, Ines Liebscher
Feb 21, 2006·Cancer Research·Christelle AdolpheBrandon Wainwright
Jan 2, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Raphaël MaréchalJean-Luc Van Laethem
Mar 11, 2016·Molecular Cancer Therapeutics·Gessica FilocamoSimonetta Pazzaglia
Oct 26, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Marie EvangelistaFrederic J de Sauvage
Jul 30, 2009·Cancer Research·Jan-Willem Theunissen, Frederic J de Sauvage
Feb 22, 2018·Cancer Research·Muhammad M RahmanGraham W Neill
Mar 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yu-Zhen FengIkuo Konishi
Jun 19, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Motohisa TadaMasao Omata
May 26, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Harvey WongStephen E Gould
Feb 9, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Patricia M LoRussoDaniel D Von Hoff
Sep 4, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Juliane M JürgensmeierRoy S Herbst
Jul 6, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Noah A BrownBryan L Betz
Feb 14, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Renata E GordonZeng-Jie Yang
Jan 17, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Atsushi OtsukaReinhard Dummer
Nov 8, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christina DanialAnne Lynn S Chang
Jan 15, 2015·Molecular Cancer Therapeutics·Nicole Basset-SeguinFrederic J de Sauvage
Mar 7, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jasmin WellbrockWalter Fiedler
Dec 4, 2020·FEBS Letters·Nadia Arang, J Silvio Gutkind
Jan 9, 2021·Journal of Cellular Biochemistry·Julia KuehnMartin Götte
Jun 2, 2020·Seminars in Cell & Developmental Biology·Ming Ma
Jun 17, 2020·Seminars in Cell & Developmental Biology·Daniel KopinkeSaikat Mukhopadhyay
Jul 29, 2019·Translational Oncology·Madiha NiyazSyed Mudassar

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