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

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.

TRIM16 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Modulating CHIP-Mediated Degradation of RUNX2

“…Previous studies have documented the functions of TRIM16 mainly in cancer, innate immune and other physiological and pathophysiological processes ( Hatakeyama, 2017 ; Sutton et al, 2019 ). To date, the role of TRIM16 in osteogenesis is largely unknown.…”

TRIM16 Positively Regulates Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Modulating the Ubiquitination and Degradation of RUNX2

“…Previous studies have documented the functions of TRIM16 in cancer, innate immune and other physiological and pathophysiological processes [19,27]. To date, the role of TRIM16 in osteogenesis is largely unknown.…”

Stromal Cells Present in the Melanoma Niche Affect Tumor Invasiveness and Its Resistance to Therapy

“…Keratinocytes are also able to influence melanocytes and melanoma cells through factors secreted to the stroma. Under the influence of UV radiation, keratinocytes secrete tripartite motif-containing protein 16 (TRIM16) [ 46 ]. It was reported that the TRIM16 level in melanoma was lower compared to the normal melanocytes, which also correlated with a rate of lymph node metastasis in TRIM16 LOW melanoma patients.…”

“…It was reported that the TRIM16 level in melanoma was lower compared to the normal melanocytes, which also correlated with a rate of lymph node metastasis in TRIM16 LOW melanoma patients. Moreover, BRAF inhibitor treatment increased the TRIM16 production in melanoma cells, while TRIM16-deficient mice exhibited elevated incidence of metastasis compared to the control animals [ 46 , 47 ]. This study supports the thesis that keratinocyte-derived TRIM16 may inhibit melanoma metastasis ( Figure 2 ) [ 46 ].…”