title: Active nuclear IKK correlates with metastatic risk in cutaneous squamous cell carcinoma.
abstract: About 5% of all cutaneous squamous cell carcinomas (cSCCs) metastasize, which is the principal cause of death by this type of cancer. However, to date there are no reliable biomarkers that categorize those SCC patients that will progress to metastasis. Nuclear active IKKα diminishes Maspin levels in prostate cancer facilitating its metastatic potential. In this paper, we describe the immunohistochemical analysis of active IKK and Maspin in 56 metastasizing and 51 non-metastasizing primary cSCC to measure their association with cancer behaviour. We also determined the effect of inhibiting IKK activity in SCC cell growth and migration in vitro. We found that high levels of nuclear active IKK in the primary tumour are predictive of cSCC metastatic capacity, in particular when combined with poor tumour differentiation and a history of tumour recurrence. Active IKK inversely correlated with Maspin levels in cSCC tumours, and samples negative for Maspin are exclusively found in the metastatic group. Mechanistically, IKK activity regulates cellular motility and SCC cell survival. Our results indicate that nuclear active IKK is a robust biomarker to predict cSCC outcome, and suggest the possibility of targeting IKK activity as a future therapy for treating metastatic cSCC.
authors.affiliation: Department of Dermatology, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain. atoll@parcdesalutmar.cat.
authors.forename: Agusti
authors.initials: A
authors.lastname: Toll
authors.affiliation: Stem Cells and Cancer Research Laboratory, Institut Hospital del Mar Investigacions Mèdiques (IMIM), Barcelona, Spain.|Francis Crick Institute, Clare Hall Laboratory, Blanche Lane, South Mimms, EN6 3LD, Hertfordshire, UK.
authors.forename: Pol
authors.initials: P
authors.lastname: Margalef
authors.affiliation: Department of Dermatology, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain.
authors.forename: Emili
authors.initials: E
authors.lastname: Masferrer
authors.affiliation: Department of Dermatology, Hospital Universitari Vall d'Hebrón, Barcelona, Spain.
authors.forename: Carla
authors.initials: C
authors.lastname: Ferrándiz-Pulido
authors.affiliation: Pathology Department, Parc de Salut Mar. Hospital del Mar, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Gimeno
authors.affiliation: Department of Dermatology, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain.
authors.forename: Ramon Maria
authors.initials: RM
authors.lastname: Pujol
authors.affiliation: Stem Cells and Cancer Research Laboratory, Institut Hospital del Mar Investigacions Mèdiques (IMIM), Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Bigas
authors.affiliation: Stem Cells and Cancer Research Laboratory, Institut Hospital del Mar Investigacions Mèdiques (IMIM), Barcelona, Spain.
authors.forename: Lluis
authors.initials: L
authors.lastname: Espinosa
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000473:pathology*; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D018307:Neoplasms, Squamous Cell / Q000473:pathology*; D015843:Serpins / Q000378:metabolism*; D012878:Skin Neoplasms / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C085344:SERPIN-B5; D015843:Serpins; D051550:I-kappa B Kinase
keywords: Biomarkers; Cutaneous; IKK; Lymph nodes; Maspin; Metastasis; Squamous cell carcinoma