Journal article

Loss of GRHL3 leads to TARC/CCL17-mediated keratinocyte proliferation in the epidermis

Stephen J Goldie, Denny L Cottle, Fiona H Tan, Suraya Roslan, Seema Srivastava, Rhys Brady, Darren D Partridge, Alana Auden, Ian M Smyth, Stephen M Jane, Sebastian Dworkin, Charbel Darido

CELL DEATH & DISEASE | NATURE PUBLISHING GROUP | Published : 2018

Abstract

Identifying soluble factors that influence epidermal integrity is critical for the development of preventative and therapeutic strategies for disorders such as ichthyosis, psoriasis, dermatitis and epidermal cancers. The transcription factor Grainyhead-like 3 (GRHL3) is essential for maintaining barrier integrity and preventing development of cutaneous squamous cell carcinoma (SCC); however, how loss of this factor, which in the skin is expressed exclusively within suprabasal epidermal layers triggers proliferation of basal keratinocytes, had thus far remained elusive. Our present study identifies thymus and activation-regulated chemokine (TARC) as a novel soluble chemokine mediator of kerat..

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Grants

Awarded by Australian National Health and Medical Research (NHMRC)


Awarded by Association for International Cancer Research (AICR)


Awarded by Victorian Cancer Agency


Funding Acknowledgements

The authors would like to acknowledge the assistance of Stephen Cody from Monash Micro Imaging, Monash University and The Monash Histology Platform (MHP) for assistance with the immunostainings. This work was supported by grants from the Peel Trust, UK and the Berkeley Fellowship, UK to S.J.G., and a publication award from the School of Life Sciences, La Trobe University to S.D., and by grants from the Australian National Health and Medical Research (NHMRC, APP1049870, APP1106697), from The Association for International Cancer Research (AICR, 11-0060) and by Fellowships from the Victorian Cancer Agency (Clare Oliver Memorial, COF11_04 and Mid-Career, MCRF16017) to C.D.