Predictors of Basal Cell Carcinoma in High-Risk Patients in the VATTC (VA Topical Tretinoin Chemoprevention) Trial

Association Between Epidermodysplasia Verruciformis-Associated Human Papillomavirus DNA in Plucked Eyebrow Hair and Solar Keratoses

Intake of Alcohol May Modify the Risk for Non-Melanoma Skin Cancer: Results of a Large Danish Prospective Cohort Study

The Mitochondrial DNA Common Deletion Is Present in Most Basal and Squamous Cell Carcinoma Samples Isolated by Laser Capture Microdissection but Generally at Reduced Rather than Increased Levels

Tumor of follicular infundibulum–associated neoplasms

Shingles and pneumonia and risk of cutaneous basal and squamous cell carcinoma

Progress in Dermatology: Cutaneous Oncology in Organ Transplant Recipients: Meeting the Challenge of Squamous Cell Carcinoma

Section 11: Evaluation and Management of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

Characterization of intractable diarrhea resulting from vismodegib treatment for basal cell nevus syndrome

Cells to Surgery Quiz: December 2018

Elevated YAP and Its Downstream Targets CCN1 and CCN2 in Basal Cell Carcinoma: Impact on Keratinocyte Proliferation and Stromal Cell Activation

Ocular hazards of blue-light therapy in dermatology

Hedgehog (HH) signaling in the epidermis is primarily mediated by the zinc finger transcription factors GLI1 and GLI2. Exquisite regulation of HH/GLI signaling is crucial for proper specification of the epidermal lineage and development of its derivatives, whereas dysregulation of HH/GLI signaling disrupts tissue homeostasis and causes basal cell carcinoma (BCC). Similarly, bone morphogenetic proteins (BMPs) and activins have been described as key signaling factors in the complex regulation of epidermal fate decisions, although their precise interplay with HH/GLI is largely elusive. Here we show that, in human epidermal cells, expression of the activin/BMP antagonist follistatin (FST) is predominantly up-regulated by the HH effector GLI2. Consistently, we found strong FST expression in the outer root sheath of human hair follicles and BCC. Detailed promoter analysis showed that two sequences with homology to the GLI consensus binding site are required for GLI2-mediated activation. Interestingly, activation of the FST promoter is highly GLI2-specific, because neither GLI1 nor GLI3 can significantly increase FST transcription. GLI2 specificity requires the presence of a 518-bp fragment in the proximal FST promoter region. On the protein level, sequences C-terminal to the zinc finger are responsible for GLI2-specific activation of FST transcription, pointing to the existence of GLI-interacting cofactors that modulate GLI target specificity. Our results reveal a key role of GLI2 in activation of the activin/BMP antagonist FST in response to HH signaling and provide new evidence for a regulatory interaction between HH and activin/BMP signaling in hair follicle development and BCC.

Lack of Evidence for Activation of the Hedgehog Pathway in Psoriasis

WNT Signaling in Cutaneous Squamous Cell Carcinoma: A Future Treatment Strategy?

Report of the Topical Calcineurin Inhibitor Task Force of the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology