The retinoid signalling molecule, TRIM16, is repressed during squamous cell carcinoma skin carcinogenesis in vivo and reduces skin cancer cell migration in vitro. / Cheung, Belamy B.; Koach, Jessica; Tan, Owen; Kim, Patrick; Bell, Jessica L.; D'andreti, Carla; Sutton, Selina; Malyukova, Alena; Sekyere, Eric; Norris, Murray; Haber, Michelle; Kavallaris, Maria; Cunningham, Anne M.; Proby, Charlotte; Leigh, Irene; Wilmott, James S.; Cooper, Caroline L.; Halliday, Gary M.; Scolyer, Richard A.; Marshall, Glenn M.
In: Journal of Pathology, Vol. 226, No. 3, 02.2012, p. 451-462.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The retinoid signalling molecule, TRIM16, is repressed during squamous cell carcinoma skin carcinogenesis in vivo and reduces skin cancer cell migration in vitro
A1 - Cheung,Belamy B.
A1 - Koach,Jessica
A1 - Tan,Owen
A1 - Kim,Patrick
A1 - Bell,Jessica L.
A1 - D'andreti,Carla
A1 - Sutton,Selina
A1 - Malyukova,Alena
A1 - Sekyere,Eric
A1 - Norris,Murray
A1 - Haber,Michelle
A1 - Kavallaris,Maria
A1 - Cunningham,Anne M.
A1 - Proby,Charlotte
A1 - Leigh,Irene
A1 - Wilmott,James S.
A1 - Cooper,Caroline L.
A1 - Halliday,Gary M.
A1 - Scolyer,Richard A.
A1 - Marshall,Glenn M.
AU - Cheung,Belamy B.
AU - Koach,Jessica
AU - Tan,Owen
AU - Kim,Patrick
AU - Bell,Jessica L.
AU - D'andreti,Carla
AU - Sutton,Selina
AU - Malyukova,Alena
AU - Sekyere,Eric
AU - Norris,Murray
AU - Haber,Michelle
AU - Kavallaris,Maria
AU - Cunningham,Anne M.
AU - Proby,Charlotte
AU - Leigh,Irene
AU - Wilmott,James S.
AU - Cooper,Caroline L.
AU - Halliday,Gary M.
AU - Scolyer,Richard A.
AU - Marshall,Glenn M.
PY - 2012/2
Y1 - 2012/2
N2 - <p>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 (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</p>
AB - <p>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 (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</p>
KW - TRIM16
KW - tripartite motif protein
KW - squamous cell carcinoma
KW - vimentin
KW - E2F1
KW - B-BOX PROTEIN
KW - CHROMOSOME 17P
KW - ACID
KW - ISOTRETINOIN
KW - REGULATOR
KW - E2F-1
KW - LINES
KW - RISK
KW - BETA
U2 - 10.1002/path.2986
DO - 10.1002/path.2986
M1 - Article
JO - Journal of Pathology
JF - Journal of Pathology
SN - 0022-3417
IS - 3
VL - 226
SP - 451
EP - 462
ER -