The retinoid signalling molecule, TRIM16, is repressed during squamous cell carcinoma skin carcinogenesis in vivo and reduces skin cancer cell migration in vitro

Abstract

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.

TRIM16 suppresses the progression of prostate tumors by inhibiting the Snail signaling pathway

“…The C-terminus of TRIM16 contains an RFP-like or B30.2/SPRY (B30.2) domain. TRIM16 expression is induced in different types of cancer, when the cancer cell is forced to proceed down a differentiation pathway (12,13,24,25); however, the role of TRIM16 in prostate cancer has not yet been clarified.…”

TRIMs and Galectins Globally Cooperate and TRIM16 and Galectin-3 Co-direct Autophagy in Endomembrane Damage Homeostasis

“…Given the connections to autophagic machinery via TRIM16, the role of Galectin-3 in control of bacteria or pathology associated with mycobacterial infection can now be mechanistically linked to the TRIM-driven process of precision autophagy (Kimura et al, 2016), which differs from bulk autophagy. TRIM16 is also known as estrogen-responsive B box protein, and its role in cancer (a general property of TRIMs (Hatakeyama, 2011)) has been linked to specific effects on immune signaling (Sutton et al, 2014), cell survival (Kim et al, 2013), cell migration and metastasis (Marshall et al, 2010; Sutton et al, 2014) through various mechanisms, including measures of membrane repair (Cheung et al, 2012; Marshall et al, 2010), with the latter potentially overlapping with the processes described in this work.…”

TRIM16 inhibits neuroblastoma cell proliferation through cell cycle regulation and dynamic nuclear localization

“…TRIM16 is a ubiquitously expressed, predominately cytoplasmic protein, with mRNA expression levels highest in the embryonic brain and in adult testes 3 . We have previously demonstrated that overexpression of TRIM16 causes decreased proliferation in neuroblastoma and in lung, breast and skin cancer cell lines 4 - 7 . Overexpression of TRIM16 is able to enhance retinoid-induced differentiation and causes downregulation of cell cycle factors E2F1 and pRB.…”