Published in:
Open Access
01-09-2019 | Metastasis | Original Article – Cancer Research
Heterozygous loss of keratinocyte TRIM16 expression increases melanocytic cell lesions and lymph node metastasis
Authors:
Selina K. Sutton, Belamy B. Cheung, Hassina Massudi, Owen Tan, Jessica Koach, Chelsea Mayoh, Daniel R. Carter, Glenn M. Marshall
Published in:
Journal of Cancer Research and Clinical Oncology
|
Issue 9/2019
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Abstract
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.