No conflicts of interest were declared.
The retinoid signalling molecule, TRIM16, is repressed during squamous cell carcinoma skin carcinogenesis in vivo and reduces skin cancer cell migration in vitro†
Article first published online: 18 OCT 2011
Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 226, Issue 3, pages 451–462, February 2012
How to Cite
Cheung, B. B., Koach, J., Tan, O., Kim, P., Bell, J. L., D'andreti, C., Sutton, S., Malyukova, A., Sekyere, E., Norris, M., Haber, M., Kavallaris, M., Cunningham, A. M., Proby, C., Leigh, I., Wilmott, J. S., Cooper, C. L., Halliday, G. M., Scolyer, R. A. and Marshall, G. M. (2012), The retinoid signalling molecule, TRIM16, is repressed during squamous cell carcinoma skin carcinogenesis in vivo and reduces skin cancer cell migration in vitro. J. Pathol., 226: 451–462. doi: 10.1002/path.2986
- Issue published online: 16 JAN 2012
- Article first published online: 18 OCT 2011
- Accepted manuscript online: 18 AUG 2011 09:46AM EST
- Manuscript Accepted: 12 AUG 2011
- Manuscript Revised: 4 AUG 2011
- Manuscript Received: 14 MAY 2011
- National Health and Medical Research Council Australia
- Cancer Institute NSW
- Cancer Council NSW
- Re-use of this article is permitted in accordance with the Terms and Conditions set out at [http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms]
- tripartite motif protein;
- squamous cell carcinoma;
Retinoid therapy is used for chemo-prevention in immuno-suppressed patients at high risk of developing skin cancer. The retinoid signalling molecule, tripartite motif protein 16 (TRIM16), is a regulator of keratinocyte differentiation and a tumour suppressor in retinoid-sensitive neuroblastoma. We sought to determine the role of TRIM16 in skin squamous cell carcinoma (SCC) pathogenesis. We have shown that TRIM16 expression was markedly reduced during the histological progression from normal skin to actinic keratosis and SCC. SCC cell lines exhibited lower cytoplasmic and nuclear TRIM16 expression compared with primary human keratinocyte (PHK) cells due to reduced TRIM16 protein stability. Overexpressed TRIM16 translocated to the nucleus, inducing growth arrest and cell differentiation. In SCC cells, TRIM16 bound to and down regulated nuclear E2F1, this is required for cell replication. Retinoid treatment increased nuclear TRIM16 expression in retinoid-sensitive PHK cells, but not in retinoid-resistant SCC cells. Overexpression of TRIM16 reduced SCC cell migration, which required the C-terminal RET finger protein (RFP)-like domain of TRIM16. The mesenchymal intermediate filament protein, vimentin, was directly bound and down-regulated by TRIM16 and was required for TRIM16-reduced cell migration. Taken together, our data suggest that loss of TRIM16 expression plays an important role in the development of cutaneous SCC and is a determinant of retinoid sensitivity. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.