Notch signaling is significantly suppressed in basal cell carcinomas and activation induces basal cell carcinoma cell apoptosis

Shi,Feng‑Tao; Yu,Mei; Zloty,David; Bell,Robert   H.; Wang,Eddy; Akhoundsadegh,Noushin; Leung,Gigi; Haegert,Anne; Carr,Nicholas; Shapiro,Jerry; McElwee,Kevin  J.

doi:10.3892/mmr.2017.6163

Notch signaling is significantly suppressed in basal cell carcinomas and activation induces basal cell carcinoma cell apoptosis

Authors:
- Feng‑Tao Shi
- Mei Yu
- David Zloty
- Robert H. Bell
- Eddy Wang
- Noushin Akhoundsadegh
- Gigi Leung
- Anne Haegert
- Nicholas Carr
- Jerry Shapiro
- Kevin J. McElwee
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Affiliations: Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC V5Z 4E8, Canada, Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC V6H 3Z6, Canada, Department of Surgery, University of British Columbia, Vancouver, BC V5Z 1M9, Canada
Published online on: February 2, 2017 https://doi.org/10.3892/mmr.2017.6163
Pages: 1441-1454
Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

A subset of basal cell carcinomas (BCCs) are directly derived from hair follicles (HFs). In some respects, HFs can be defined as ‘ordered’ skin appendage growths, while BCCs can be regarded as ‘disordered’ skin appendage growths. The aim of the present study was to examine HFs and BCCs to define the expression of common and unique signaling pathways in each skin appendage. Human nodular BCCs, along with HFs and non‑follicular skin epithelium from normal individuals, were examined using microarrays, qPCR, and immunohistochemistry. Subsequently, BCC cells and root sheath keratinocyte cells from HFs were cultured and treated with Notch signaling peptide Jagged1 (JAG1). Gene expression, protein levels, and cell apoptosis susceptibility were assessed using qPCR, immunoblotting, and flow cytometry, respectively. Specific molecular mechanisms were found to be involved in the process of cell self‑renewal in the HFs and BCCs, including Notch and Hedgehog signaling pathways. However, several key Notch signaling factors showed significant differential expression in BCCs compared with HFs. Stimulating Notch signaling with JAG1 induced apoptosis of BCC cells by increasing Fas ligand expression and downstream caspase-8 activation. The present study showed that Notch signaling pathway activity is suppressed in BCCs, and is highly expressed in HFs. Elements of the Notch pathway could, therefore, represent targets for the treatment of BCCs and potentially in hair follicle engineering.

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