scholarly journals Roles of the Hedgehog Signaling Pathway in Skin Development, Homeostasis and Cancer

2017 ◽  
Author(s):  
Yoshinori Abe ◽  
Nobuyuki Tanaka
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Basal Cell ◽  
Hedgehog Signaling ◽  
Current Knowledge ◽  
Skin Development ◽  
Morphogenetic Protein ◽  
Hh Signaling

The epidermis is the outermost layer of skin and provides a protective barrier against environmental insults. It is a rapidly renewing tissue undergoing constant regeneration, maintained by several types of stem cells. Hedgehog (HH) ligands activate one of the fundamental signaling pathways that contribute to epidermal development, homeostasis and repair. The HH pathway interacts with other signal transduction pathways such as those activated by Wnt and bone morphogenetic protein. Furthermore, aberrant activation of HH signaling is associated with various tumors, including basal cell carcinoma. Therefore, an understanding of the regulatory mechanisms of the HH signaling pathway is important to elucidate fundamental mechanisms underlying both organogenesis and carcinogenesis. In this review, we discuss the role of the HH signaling pathway in skin development, homeostasis and basal cell carcinoma formation, providing an update of current knowledge in this field.

scholarly journals The role of hedgehog signaling in gastric cancer: molecular mechanisms, clinical potential, and perspective

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Yan Xu ◽  
Shumei Song ◽  
Zhenning Wang ◽  
Jaffer A. Ajani
Keyword(s):  
Gastric Cancer ◽  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Hedgehog Signaling ◽  
Molecular Mechanisms ◽  
Physiologic Function ◽  
Hh Signaling ◽  
Effective Drugs

AbstractPatients with advanced gastric cancer usually have a poor prognosis and limited therapeutic options. Overcoming this challenge requires novel targets and effective drugs. The Hedgehog (Hh) signaling pathway plays a crucial role in the development of the gastrointestinal tract and maintenance of the physiologic function of the stomach. Aberrantly activated Hh signaling is implicated in carcinogenesis as well as maintenance of cancer stem cells. Somatic mutations in the components of Hh signaling (PTCH1 and SMO) have been shown to be a major cause of basal cell carcinoma, and dozens of Hh inhibitors have been developed. To date, two inhibitors (GDC-0449 and LDE225) have been approved by the U.S. Food and Drug Administration to treat basal cell carcinoma and medulloblastoma. Here, we review the role of the Hh signaling in the carcinogenesis and progression of gastric cancer and summarize recent findings on Hh inhibitors in gastric cancer. Hedgehog signaling is often aberrantly activated and plays an important role during inflammation and carcinogenesis of gastric epithelial cells. Further study of the precise mechanisms of Hh signaling in this disease is needed for the validation of therapeutic targets and evaluation of the clinical utility of Hh inhibitors for gastric cancer.

scholarly journals DDX5 Silencing Suppresses the Migration of Basal cell Carcinoma Cells by Downregulating JAK2/STAT3 Pathway

2019 ◽  
Vol 18 ◽  
pp. 153303381989225 ◽  
Author(s):  
Zhe Quan ◽  
Bei-bei Zhang ◽  
Fang Yin ◽  
Jiru Du ◽  
Yuan-ting Zhi ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Hedgehog Signaling ◽  
Human Cancer ◽  
Carcinoma Cells ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Migration And Invasion ◽  
Stat3 Pathway

Basal cell carcinoma is driven by the aberrant activation of hedgehog signaling. DEAD (Asp-Glu-Ala-Asp) box protein 5 is frequently overexpressed in human cancer cells and associated with the tumor growth and invasion. The purpose of this study was to investigate the role of DEAD (Asp-Glu-Ala-Asp) box protein 5 in the growth, migration, and invasion of basal cell carcinoma. The role of DEAD (Asp-Glu-Ala-Asp) box protein 5 was detected by quantitative real-time polymerase chain reaction, Western blot, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay in basal cell carcinoma cells. The associations between JAK2/STAT3 pathway and DEAD (Asp-Glu-Ala-Asp) box protein 5 were analyzed in basal cell carcinoma cells. Results showed that DEAD (Asp-Glu-Ala-Asp) box protein 5 is overexpressed in basal cell carcinoma cells. DEAD (Asp-Glu-Ala-Asp) box protein 5 knockdown inhibited the migration and invasion of basal cell carcinoma cells. DEAD (Asp-Glu-Ala-Asp) box protein 5 knockdown increased the apoptosis of basal cell carcinoma cells induced by tunicamycin. Results found that DEAD (Asp-Glu-Ala-Asp) box protein 5 knockdown increased JAK2 and STAT3 expression in basal cell carcinoma cells. JAK2 inhibitor decreased STAT3 expression and abolished the inhibitory effects of DEAD (Asp-Glu-Ala-Asp) box protein 5 silencing on migration and invasion in basal cell carcinoma cells. In conclusion, these results indicate that DEAD (Asp-Glu-Ala-Asp) box protein 5 is a potential target for inhibiting basal cell carcinoma cells growth, migration, and invasion by downregulating JAK2/STAT3 pathway.

scholarly journals Vismodegib: The Proof of Concept in Basal Cell Carcinoma

2014 ◽  
Vol 8 ◽  
pp. CMO.S14569 ◽  
Author(s):  
Narjiss Berrada ◽  
Siham Lkhoyali ◽  
Hind Mrabti ◽  
Hassan Errihani
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Basal Cell ◽  
Hedgehog Signaling ◽  
Treatment Options ◽  
Locally Advanced ◽  
Scientific Data ◽  
Hedgehog Signaling Pathway ◽  
Proof Of Concept

Although basal cell carcinoma (BCC) is the most common cancer worldwide, its metastatic dissemination is exceptional. Before 2012, we had a few treatment options available for metastatic or locally advanced cases. Management of these patients was complicated due to the lack of scientific data, the deterioration of a patient's general status, the patient's advanced age, and the presence of multiple comorbidities. The hedgehog signaling pathway is dysregulated in BCC. The exploration of this signaling pathway yielded to a major milestone in the treatment of advanced BCC. Vismodegib (GDC-0449), an oral small-molecule agent that targets the Hedgehog signaling pathway, demonstrates high levels of activity in clinical trials. It was approved in January 2012 for the treatment of locally advanced or metastatic BCC. Vismodegib confirms, once again, the interest in exploring the signal transduction pathways in cancers.

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