Expression of nuclear survivin in normal skin and squamous cell carcinoma: a possible role in tumour invasion

• Published in: British journal of cancer Vol. 110; no. 1; pp. 199 - 207
• Main Authors: Dallaglio, K, Petrachi, T, Marconi, A, Truzzi, F, Lotti, R, Saltari, A, Morandi, P, Puviani, M, Maiorana, A, Pincelli, C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.01.2014; Nature Publishing Group
• Subjects: 631/208/199; 631/67/1813/1352; 631/80/84/2336; Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antibodies; Apoptosis; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell cycle; Cell division; Cell Lineage; Cell Nucleus - metabolism; Child; Child, Preschool; Cytoplasm; Dermatology; Drug Resistance; Epidemiology; Humans; Infant; Infant, Newborn; Inhibitor of Apoptosis Proteins - biosynthesis; Keratinocytes - metabolism; Localization; Medical sciences; Melanoma; Middle Aged; Molecular Diagnostics; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Invasiveness; Neoplasm Proteins - biosynthesis; Oncology; Skin - metabolism; Skin cancer; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Stem cells; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; Young Adult; United States > US; Italy; survivin; differentiation; keratinocyte; tumour; skin; nuclear; squamous cell carcinoma; Skin disease; Squamous cell carcinoma; Basal cell carcinoma; Keratinocyte cancer; Tumorous infiltration; Malignant tumor; Metastasis; Survivin; Cell differentiation; Invasion; Skin cancer; Skin squamous cell carcinoma; Cancerology; Apoptosis inhibitory protein; Keratinocyte; Skin; Differentiation; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2013.697

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. Conclusion: High survivin expression and the subcellular localisation of survivin correlate with keratinocyte differentiation and are associated with undifferentiated and more invasive SCC phenotype.