Heterozygous loss of keratinocyte TRIM16 expression increases melanocytic cell lesions and lymph node metastasis

Sutton, SK; Cheung, BB; Massudi, H; Tan, O; Koach, J; Mayoh, C; Carter, DR; Marshall, GM

Heterozygous loss of keratinocyte TRIM16 expression increases melanocytic cell lesions and lymph node metastasis

Sutton, SK Cheung, BB Massudi, H Tan, O Koach, J Mayoh, C Carter, DR Marshall, GM

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Publication Type:: Journal Article
Citation:: Journal of Cancer Research and Clinical Oncology, 2019, 145 (9), pp. 2241 - 2250
Issue Date:: 2019-09-04

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Field	Value	Language
dc.contributor.author	Sutton, SK	en_US
dc.contributor.author	Cheung, BB	en_US
dc.contributor.author	Massudi, H	en_US
dc.contributor.author	Tan, O	en_US
dc.contributor.author	Koach, J	en_US
dc.contributor.author	Mayoh, C	en_US
dc.contributor.author	Carter, DR	en_US
dc.contributor.author	Marshall, GM	en_US
dc.date.available	2019-07-16	en_US
dc.date.issued	2019-09-04	en_US
dc.identifier.citation	Journal of Cancer Research and Clinical Oncology, 2019, 145 (9), pp. 2241 - 2250	en_US
dc.identifier.issn	0171-5216	en_US
dc.identifier.uri	http://hdl.handle.net/10453/138259
dc.description.abstract	© 2019, The Author(s). Purpose: The tripartite motif (TRIM)16 acts as a tumour suppressor in both squamous cell carcinoma (SCC) and melanoma. TRIM16 is known to be secreted by keratinocytes, but no studies have been reported yet to assess the relationship between TRIM16 keratinocyte expression and melanoma development. Methods: To study the role of TRIM16 in skin cancer development, we developed a keratinocyte TRIM16-specific knockout mouse model, and used the classical two-stage skin carcinogenesis challenge method, to assess the loss of keratinocyte TRIM16 on both papilloma, SCC and melanoma development in the skin after topical carcinogen treatment. Results: Heterozygous, but not homozygous, TRIM16 knockout mice exhibited an accelerated development of skin papillomas and melanomas, larger melanoma lesions and an increased potential for lymph node metastasis. Conclusion: This study provides the first evidence that keratinocyte loss of the putative melanoma tumour suppressor protein, TRIM16, enhances melanomagenesis. Our data also suggest that TRIM16 expression in keratinocytes is involved in cross talk between keratinocytes and melanocytes, and has a role in melanoma tumorigenesis.	en_US
dc.relation.ispartof	Journal of Cancer Research and Clinical Oncology	en_US
dc.relation.isbasedon	10.1007/s00432-019-02981-5	en_US
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject.classification	Oncology & Carcinogenesis	en_US
dc.subject.mesh	Lymph Nodes	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Keratinocytes	en_US
dc.subject.mesh	Melanocytes	en_US
dc.subject.mesh	Skin	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Knockout	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Melanoma	en_US
dc.subject.mesh	Carcinoma, Squamous Cell	en_US
dc.subject.mesh	Skin Neoplasms	en_US
dc.subject.mesh	Cell Transformation, Neoplastic	en_US
dc.subject.mesh	Lymphatic Metastasis	en_US
dc.subject.mesh	Carrier Proteins	en_US
dc.subject.mesh	Gene Expression Regulation, Neoplastic	en_US
dc.subject.mesh	Loss of Heterozygosity	en_US
dc.title	Heterozygous loss of keratinocyte TRIM16 expression increases melanocytic cell lesions and lymph node metastasis	en_US
dc.type	Journal Article
utslib.citation.volume	9	en_US
utslib.citation.volume	145	en_US
utslib.for	1112 Oncology and Carcinogenesis	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	closed_access	*
pubs.issue	9	en_US
pubs.publication-status	Published	en_US
pubs.volume	145	en_US

Abstract:

© 2019, The Author(s). Purpose: The tripartite motif (TRIM)16 acts as a tumour suppressor in both squamous cell carcinoma (SCC) and melanoma. TRIM16 is known to be secreted by keratinocytes, but no studies have been reported yet to assess the relationship between TRIM16 keratinocyte expression and melanoma development. Methods: To study the role of TRIM16 in skin cancer development, we developed a keratinocyte TRIM16-specific knockout mouse model, and used the classical two-stage skin carcinogenesis challenge method, to assess the loss of keratinocyte TRIM16 on both papilloma, SCC and melanoma development in the skin after topical carcinogen treatment. Results: Heterozygous, but not homozygous, TRIM16 knockout mice exhibited an accelerated development of skin papillomas and melanomas, larger melanoma lesions and an increased potential for lymph node metastasis. Conclusion: This study provides the first evidence that keratinocyte loss of the putative melanoma tumour suppressor protein, TRIM16, enhances melanomagenesis. Our data also suggest that TRIM16 expression in keratinocytes is involved in cross talk between keratinocytes and melanocytes, and has a role in melanoma tumorigenesis.

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http://hdl.handle.net/10453/138259