RT Journal Article
T1 CYLD regulates keratinocyte differentiation and skin cancer progression in humans
A1 Alameda, Josefa P.
A1 Fernández Aceñero, María Jesús
A1 Moreno Maldonado, Rodolfo
A1 Navarro, Manuel
A1 Quintana, R.
A1 Page, Angustias
A1 Ramírez, Ángel
A1 Bravo Moral, Ana María
A1 Llanos Casanova, M.
K1 CYLD
K1 Keratinocyte differentiation
K1 Skin cancer
K1 Skin equivalents
AB CYLD is a gene mutated in familial cylindromatosis and related diseases, leading to the development of skin appendages tumors. Although the deubiquitinase CYLD is a skin tumor suppressor, its role in skin physiology is unknown. Using skin organotypic cultures as experimental model to mimic human skin, we have found that CYLD acts as a regulator of epidermal differentiation in humans through the JNK signaling pathway. We have determined the requirement of CYLD for the maintenance of epidermal polarity, keratinocyte differentiation and apoptosis. We show that CYLD overexpression increases keratinocyte differentiation while CYLD loss of function impairs epidermal differentiation. In addition, we describe the important role of CYLD in the control of human non-melanoma skin cancer progression. Our results show the reversion of the malignancy of human squamous cell carcinomas that express increased levels of CYLD, while its functional inhibition enhances the aggressiveness of these tumors which progress toward spindle cell carcinomas. We have found that the mechanisms through which CYLD regulates skin cancer progression include the control of tumor differentiation, angiogenesis and cell survival. These findings of the role of CYLD in human skin cancer prognosis make our results relevant from a therapeutic point of view, and open new avenues for exploring novel cancer therapies
PB Nature Publishing Group
YR 2011
FD 2011
LK http://hdl.handle.net/10347/22318
UL http://hdl.handle.net/10347/22318
LA eng
NO Alameda, J. P., Fernandez-Acenero, M. J., Moreno-Maldonado, R., Navarro, M., Quintana, R., Page, A., ... & Casanova, M. L. (2011). CYLD regulates keratinocyte differentiation and skin cancer progression in humans. Cell death & disease, 2(9), e208-e208.
NO This work was funded by grants from the Ministerio de Ciencia e Innovación PI06/1233 and PI10/01480 to MLC, and SAF2010-22156 to AR
DS Minerva
RD 22 abr 2026