title: Expression of nuclear survivin in normal skin and squamous cell carcinoma: a possible role in tumour invasion.
abstract: BACKGROUND
  Survivin is detected in few adult normal cells and it is highly expressed in cancer. Nuclear survivin facilitates cell cycle entry, whereas the mitochondrial pool protects cells from apoptosis. Survivin is overexpressed in keratinocyte stem cells (KSCs) and protects them from apoptosis.
  
  
  METHODS
  As KSCs are at the origin of squamous cell carcinoma (SCC), we evaluated survivin expression in normal and cancerous skin in vivo by immunohistochemistry and western blotting. HaCaT cells overexpressing survivin and wound-healing assay are used. Analysis of variance and Student's T-tests are used for statistical analysis.
  
  
  RESULTS
  Survivin is localised in both the cytoplasm and nucleus of normal adult and young keratinocytes. Nuclear survivin is detected in one every 10 of 11 basal keratinocytes. When present in suprabasal cells, nuclear survivin is coexpressed with K10 but not with K15 or p75-neurotrophin receptor (p75NTR), a transit amplifying cell marker. Nuclear, but not cytoplasmic, survivin expression markedly increases in actinic keratosis and in SCC in situ, as compared with normal epidermis, and it is highest in poorly differentiated SCC. In SCC tumours, nuclear survivin-positive cells are mainly K10/p75NTR-negative and K15-positive. In poorly differentiated tumours, survivin mostly localises in the deep infiltrating areas. When overexpressed in keratinocytes, survivin increases cell migration.
  
  
  CONCLUSIONS
  High survivin expression and the subcellular localisation of survivin correlate with keratinocyte differentiation and are associated with undifferentiated and more invasive SCC phenotype.
authors.affiliation: Laboratory of Cutaneous Biology, Institute of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy.
authors.forename: K
authors.initials: K
authors.lastname: Dallaglio
authors.affiliation: Laboratory of Cutaneous Biology, Institute of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Petrachi
authors.affiliation: Laboratory of Cutaneous Biology, Institute of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Marconi
authors.affiliation: Laboratory of Cutaneous Biology, Institute of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Truzzi
authors.affiliation: Laboratory of Cutaneous Biology, Institute of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Lotti
authors.affiliation: Laboratory of Cutaneous Biology, Institute of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Saltari
authors.affiliation: Laboratory of Cutaneous Biology, Institute of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Morandi
authors.affiliation: Department of Dermatology and Dermatological Surgery, Nuovo Ospedale Civile di Sassuolo, Via Francesco Ruini 2, 41049 Sassuolo Modena, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Puviani
authors.affiliation: Department of Laboratories and Pathologic Anatomy, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Maiorana
authors.affiliation: Laboratory of Cutaneous Biology, Institute of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Pincelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D019070:Cell Lineage; D002467:Cell Nucleus / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis*; D015603:Keratinocytes / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis; D012867:Skin / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D000077022:Survivin; D055815:Young Adult
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D000077022:Survivin