Do DLX3 and CD271 Protect Human Keratinocytes from Squamous Tumor Development?
Well-regulated epidermal homeostasis depends on the function of different classes of factors, such as transcription regulators and receptors. Alterations in this homeostatic balance may lead to the development of cutaneous squamous tumorigenesis. The homeobox transcription factor DLX3 is determinant...
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doaj-17bb67bb122b4bcb8c86749b94e565952020-11-25T00:19:35ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-07-012014354110.3390/ijms20143541ijms20143541Do DLX3 and CD271 Protect Human Keratinocytes from Squamous Tumor Development?Elisabetta Palazzo0Alessandra Marconi1Carlo Pincelli2Maria I. Morasso3Laboratory of Cutaneous Biology, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, 41100 Modena, ItalyLaboratory of Cutaneous Biology, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, 41100 Modena, ItalyLaboratory of Cutaneous Biology, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, 41100 Modena, ItalyLaboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USAWell-regulated epidermal homeostasis depends on the function of different classes of factors, such as transcription regulators and receptors. Alterations in this homeostatic balance may lead to the development of cutaneous squamous tumorigenesis. The homeobox transcription factor DLX3 is determinant for a p53-dependent regulation of epidermal differentiation and modulates skin carcinogenesis. The maintenance of skin homeostasis also involves the action of neurotrophins (NTs) and their receptors, Trk and CD271. While Trk receptor overexpression is a hallmark of cancer, there are conflicting data on CD271 expression and function in cutaneous SCC (cSCC). Previous studies have reported NT receptors expression in head and neck SSC (HNSCC). We show that CD271 is expressed at low levels in primary cSCC cells and the number of CD271+ cells correlates with cell cohesion in SCC spheroids. In normal epidermis, CD271 is expressed in proliferative progenitor cells and DLX3 in terminally differentiated keratinocytes. Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) increase DLX3 expression. In the absence of a functional BDNF receptor TrkB in keratinocytes, we hypothesize that the BDNF-dependent DLX3 response could be mediated via CD271. Altogether, our results support a putative CD271-DLX3 connection in keratinocytes, which might be crucial to preventing squamous skin cancer.https://www.mdpi.com/1422-0067/20/14/3541epidermal homeostasisDLX3CD271SCC |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elisabetta Palazzo Alessandra Marconi Carlo Pincelli Maria I. Morasso |
spellingShingle |
Elisabetta Palazzo Alessandra Marconi Carlo Pincelli Maria I. Morasso Do DLX3 and CD271 Protect Human Keratinocytes from Squamous Tumor Development? International Journal of Molecular Sciences epidermal homeostasis DLX3 CD271 SCC |
author_facet |
Elisabetta Palazzo Alessandra Marconi Carlo Pincelli Maria I. Morasso |
author_sort |
Elisabetta Palazzo |
title |
Do DLX3 and CD271 Protect Human Keratinocytes from Squamous Tumor Development? |
title_short |
Do DLX3 and CD271 Protect Human Keratinocytes from Squamous Tumor Development? |
title_full |
Do DLX3 and CD271 Protect Human Keratinocytes from Squamous Tumor Development? |
title_fullStr |
Do DLX3 and CD271 Protect Human Keratinocytes from Squamous Tumor Development? |
title_full_unstemmed |
Do DLX3 and CD271 Protect Human Keratinocytes from Squamous Tumor Development? |
title_sort |
do dlx3 and cd271 protect human keratinocytes from squamous tumor development? |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-07-01 |
description |
Well-regulated epidermal homeostasis depends on the function of different classes of factors, such as transcription regulators and receptors. Alterations in this homeostatic balance may lead to the development of cutaneous squamous tumorigenesis. The homeobox transcription factor DLX3 is determinant for a p53-dependent regulation of epidermal differentiation and modulates skin carcinogenesis. The maintenance of skin homeostasis also involves the action of neurotrophins (NTs) and their receptors, Trk and CD271. While Trk receptor overexpression is a hallmark of cancer, there are conflicting data on CD271 expression and function in cutaneous SCC (cSCC). Previous studies have reported NT receptors expression in head and neck SSC (HNSCC). We show that CD271 is expressed at low levels in primary cSCC cells and the number of CD271+ cells correlates with cell cohesion in SCC spheroids. In normal epidermis, CD271 is expressed in proliferative progenitor cells and DLX3 in terminally differentiated keratinocytes. Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) increase DLX3 expression. In the absence of a functional BDNF receptor TrkB in keratinocytes, we hypothesize that the BDNF-dependent DLX3 response could be mediated via CD271. Altogether, our results support a putative CD271-DLX3 connection in keratinocytes, which might be crucial to preventing squamous skin cancer. |
topic |
epidermal homeostasis DLX3 CD271 SCC |
url |
https://www.mdpi.com/1422-0067/20/14/3541 |
work_keys_str_mv |
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