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

Selina K. Sutton, Belamy B. Cheung*, Hassina Massudi, Owen Tan, Jessica Koach, Chelsea Mayoh, Daniel R. Carter, Glenn M. Marshall

*Corresponding author for this work

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)2241-2250
Number of pages10
JournalJournal of cancer research and clinical oncology
Volume145
Issue number9
DOIs
Publication statusPublished - 4 Sep 2019
Externally publishedYes

Bibliographical note

Copyright The Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Carcinogenesis
  • Keratinocyte
  • Melanoma
  • Metastasis
  • Migration
  • TRIM16

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