Ectopic expression of SOX18 in Basal cell carcinoma negatively regulates tumour progression

Rehan Villani; Seen Ling Sim; Edwige Roy; Brandon Wainwright; Mathias Francois; Kiarash Khosrotehrani

doi:10.1016/j.jdermsci.2020.04.006

Ectopic expression of SOX18 in Basal cell carcinoma negatively regulates tumour progression

J Dermatol Sci. 2020 Jun;98(3):179-185. doi: 10.1016/j.jdermsci.2020.04.006. Epub 2020 May 7.

Authors

Rehan Villani¹, Seen Ling Sim², Edwige Roy², Brandon Wainwright³, Mathias Francois⁴, Kiarash Khosrotehrani⁵

Affiliations

¹ The University of Queensland, UQ Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia. Electronic address: r.villani@uq.edu.au.
² The University of Queensland, UQ Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia.
³ The University of Queensland, Institute for Molecular Bioscience, Brisbane, QLD, Australia.
⁴ The University of Queensland, Institute for Molecular Bioscience, Brisbane, QLD, Australia; The University of Sydney, The Centenary Institute, David Richmond Program for Cardio-Vascular Research: GeneRegulation and Editing, Sydney Medical School, Royal Prince Alfred Hospital, Missenden Rd, NSW, Australia.
⁵ The University of Queensland, UQ Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia. Electronic address: k.khosrotehrani@uq.edu.au.

PMID: 32444239
DOI: 10.1016/j.jdermsci.2020.04.006

Abstract

Background: Basal Cell Carcinoma is the most common tumour and yet much remains to be determined regarding the molecular mechanisms that leads to its development. Hedgehog signal activation is sufficient for BCC induction, but the molecular mediators of BCC growth are not well understood. SoxF transcription factor Sox18 has been identified in human BCC, but its role in growth of the tumour is as yet unknown.

Objective: To determine if Sox18 is involved in the regulation of Basal Cell Carcinoma growth.

Methods: We analysed the function of Sox18 by combining a dominant negative Sox18 mouse model, Sox18^+/OP with murine BCC RESULTS: We determine that Sox18 is ectopically expressed in the epidermal cells of a murine model of Basal Cell Carcinoma. We then show that dominant negative mutation of Sox18 increases the severity of murine Basal Cell Carcinoma. Finally, decreased Hey1 in Sox18^+/OP BCC suggests Sox18 may negatively regulate BCC progression via Notch signaling.

Conclusions: These data suggest that Sox18 is a hedgehog regulated mediator of tumour suppression within Basal Cell Carcinoma epidermis.

Keywords: Basal cell carcinoma; Hedgehog; Notch; Patched1; Sox18.

MeSH terms

Animals
Carcinoma, Basal Cell / diagnosis
Carcinoma, Basal Cell / genetics*
Carcinoma, Basal Cell / pathology
Disease Models, Animal
Ectopic Gene Expression
Epidermis / pathology*
Gene Expression Regulation, Neoplastic*
Hedgehog Proteins / metabolism
Humans
Mice
Mice, Transgenic
Mutation
Patched-1 Receptor / genetics
Receptors, Notch / metabolism
SOXF Transcription Factors / genetics
SOXF Transcription Factors / metabolism*
Severity of Illness Index
Signal Transduction / genetics
Skin Neoplasms / diagnosis
Skin Neoplasms / genetics*
Skin Neoplasms / pathology

Substances

Hedgehog Proteins
Patched-1 Receptor
Ptch1 protein, mouse
Receptors, Notch
SOXF Transcription Factors
Sox18 protein, mouse