Basal Cell Carcinoma Preferentially Arises from Stem Cells Within Hair Follicle and Mechanosensory Niches

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2015 Apr 7

PMID 25842978

Citations 176

Authors

Shelby C Peterson

Markus Eberl

Alicia N Vagnozzi

Abdelmadjid Belkadi

Natalia A Veniaminova

Monique E Verhaegen

Christopher K Bichakjian

Nicole L Ward

Andrzej A Dlugosz

Sunny Y Wong

Affiliations

Soon will be listed here.

Abstract

Basal cell carcinoma (BCC) is characterized by frequent loss of PTCH1, leading to constitutive activation of the Hedgehog pathway. Although the requirement for Hedgehog in BCC is well established, the identity of disease-initiating cells and the compartments in which they reside remain controversial. By using several inducible Cre drivers to delete Ptch1 in different cell compartments in mice, we show here that multiple hair follicle stem cell populations readily develop BCC-like tumors. In contrast, stem cells within the interfollicular epidermis do not efficiently form tumors. Notably, we observed that innervated Gli1-expressing progenitors within mechanosensory touch dome epithelia are highly tumorigenic. Sensory nerves activate Hedgehog signaling in normal touch domes, while denervation attenuates touch dome-derived tumors. Together, our studies identify varying tumor susceptibilities among different stem cell populations in the skin, highlight touch dome epithelia as "hot spots" for tumor formation, and implicate cutaneous nerves as mediators of tumorigenesis.

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