title: Functional inactivation of CYLD promotes the metastatic potential of tumor epidermal cells.
abstract: CYLD is a tumor-suppressor gene mutated in the skin appendage tumors cylindromas, trichoepitheliomas, and spiradenomas. We have performed in vivo metastasis assays in nude mice and found that the loss of the deubiquitinase function of CYLD in squamous cell carcinoma (SCC) cells greatly enhances the lung metastatic capability of these cells. These metastases showed several characteristics that make them distinguishable from those carrying a functional CYLD, such as robust angiogenesis, increased expression of tumor malignancy markers of SCCs, and a decrease in the expression of the suppressor of metastasis Maspin. Restoration of Maspin expression in the epidermal SCC cells defective in CYLD deubiquitination function significantly reduces their ability to form metastases, thereby suggesting that the decrease in the levels of Maspin expression plays an important role in the acquisition of metastatic potential of these cells. In addition, we have characterized Maspin downregulation in cylindromas, trichoepitheliomas, and spiradenomas carrying functional inactivating mutations of CYLD, also providing an evidence of the correlation between impaired CYLD function and Maspin decreased expression in vivo in human tumors.
authors: Department of Molecular Oncology, CIEMAT, Madrid, Spain.
authors: Josefa P
authors: JP
authors: Alameda
authors: M Jesús
authors: MJ
authors: Fernández-Aceñero
authors: Rita M
authors: RM
authors: Quintana
authors: Angustias
authors: A
authors: Page
authors: Ángel
authors: Á
authors: Ramírez
authors: Manuel
authors: M
authors: Navarro
authors: M Llanos
authors: ML
authors: Casanova
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology*; D003546:Cysteine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D000074749:Deubiquitinating Enzyme CYLD; D004195:Disease Models, Animal; D053535:Keratin-13 / Q000235:genetics / Q000378:metabolism; D053533:Keratin-8 / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D009154:Mutation / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D053535:Keratin-13; D053533:Keratin-8; C085344:SERPIN-B5; D015843:Serpins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C511601:CYLD protein, mouse; D000074749:Deubiquitinating Enzyme CYLD; D003546:Cysteine Endopeptidases