Details

Autor(en) / Beteiligte

• Peterson, Shelby C.
• Eberl, Markus
• Vagnozzi, Alicia N.
• Belkadi, Abdelmadjid
• Veniaminova, Natalia A.
• Verhaegen, Monique E.
• Bichakjian, Christopher K.
• Ward, Nicole L.
• Dlugosz, Andrzej A.
• Wong, Sunny Y.

Titel

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

Ist Teil von

• Cell stem cell, 2015-04, Vol.16 (4), p.400-412

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •BCCs arise primarily from stem cells within hair follicle and touch dome epithelia•Stem cells in the interfollicular epidermis do not efficiently form tumors•Innervation is required for Hedgehog signaling in the touch dome•Cutaneous nerves promote tumors arising from the touch dome mechanosensory niche The cellular origin of basal cell carcinoma (BCC), the most common cancer, has been controversial. Here, Peterson et al. report that BCCs primarily arise from stem cells within hair follicle and mechanosensory touch dome epithelia and further demonstrate that cutaneous nerves maintain touch dome identity and promote tumorigenesis.