Hedgehog signalling in skin development and cancer

被引:138
作者
Athar, Mohammad
Tang, Xiuwei
Lee, Juliette L.
Kopelovich, Levy
Kim, Arianna L.
机构
[1] Columbia Univ Coll Phys & Surg, Dept Dermatol, New York, NY 10032 USA
[2] Stanford Univ, Dept Dermatol, Stanford, CA 94305 USA
[3] NCI, Div Canc Prevent, Bethesda, MD 20892 USA
关键词
BCC; cancer; development; skin; sonic hedgehog; stem cell;
D O I
10.1111/j.1600-0625.2006.00473.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Basal cell carcinoma (BCC) is the most common human malignancy, affecting 750 000 Americans each year. The understanding of mutations that are known to activate hedgehog (Hh) signalling pathway genes, including PATCHED (PTCH), sonic hedgehog (Shh) and smoothened (Smo), has substantially expanded our current understanding of the genetic basis of BCC development. The Hh signalling pathway is one of the most fundamental signal transduction pathways in embryonic development. In skin, the Shh pathway is crucial for maintaining stem cell population, and for regulating hair follicle and sebaceous gland development. This pathway plays a minimal role in adult tissues, but is known to be activated in many neoplasms, including those arising in the skin. In this review, we attempt to summarize the results of published studies on some important aspects of the Shh pathway and its involvement in skin development and carcinogenesis. We also provide a description of various animal models that have been developed, based on our knowledge of the Shh pathway in human skin cancers. Additionally, we include a brief description of studies conducted in our laboratory and by others on the chemoprevention of BCCs. This review therefore provides a current understanding of the role of the Shh pathway in skin development and neoplasia. It also provides a basis for the molecular target-based chemoprevention and therapeutic management of skin cancer.
引用
收藏
页码:667 / 677
页数:11
相关论文
共 65 条
[11]   Edar signaling in the control of hair follicle development [J].
Botchkarev, VA ;
Fessing, MY .
JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS, 2005, 10 (03) :247-251
[12]   MIM/BEG4, a Sonic hedgehog-responsive gene that potentiates Gli-dependent transcription [J].
Callahan, CA ;
Ofstad, T ;
Horng, L ;
Wang, JK ;
Zhen, HH ;
Coulombe, PA ;
Oro, AE .
GENES & DEVELOPMENT, 2004, 18 (22) :2724-2729
[13]   Essential role for Sonic hedgehog during hair follicle morphogenesis [J].
Chiang, C ;
Swan, RZ ;
Grachtchouk, M ;
Bolinger, M ;
Ying, LTT ;
Robertson, EK ;
Cooper, MK ;
Gaffield, W ;
Westphal, H ;
Beachy, PA ;
Dlugosz, AA .
DEVELOPMENTAL BIOLOGY, 1999, 205 (01) :1-9
[14]   Desert hedgehog (Dhh) gene is required in the mouse testis for formation of adult-type Leydig cells and normal development of peritubular cells and seminiferous tubules [J].
Clark, AM ;
Garland, KK ;
Russell, LD .
BIOLOGY OF REPRODUCTION, 2000, 63 (06) :1825-1838
[15]   Basal cell carcinoma: biology, morphology and clinical implications [J].
Crowson, AN .
MODERN PATHOLOGY, 2006, 19 :S127-S147
[16]   Gli proteins up-regulate the expression of basonuclin in basal cell carcinoma [J].
Cui, CH ;
Elsam, T ;
Tian, QJ ;
Seykora, JT ;
Grachtchouk, M ;
Dlugosz, A ;
Tseng, H .
CANCER RESEARCH, 2004, 64 (16) :5651-5658
[17]   Chemoprevention of human skin cancer [J].
Einspahr, JG ;
Stratton, SP ;
Bowden, GT ;
Alberts, DS .
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2002, 41 (03) :269-285
[18]   Immunosuppressants and skin cancer in transplant patients: Focus on rapamycin [J].
Euvrard, S ;
Ulrich, C ;
Lefrancois, N .
DERMATOLOGIC SURGERY, 2004, 30 (04) :628-633
[19]   Sonic hedgehog opposes epithelial cell cycle arrest [J].
Fan, HR ;
Khavari, PA .
JOURNAL OF CELL BIOLOGY, 1999, 147 (01) :71-76
[20]   Induction of basal cell carcinoma features in transgenic human skin expressing Sonic Hedgehog [J].
Fan, HR ;
Oro, AE ;
Scott, MP ;
Khavari, PA .
NATURE MEDICINE, 1997, 3 (07) :788-792