+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Notch Cooperates with Survivin to Maintain Stemness and to Stimulate Proliferation in Human Keratinocytes during Ageing



Notch Cooperates with Survivin to Maintain Stemness and to Stimulate Proliferation in Human Keratinocytes during Ageing



International Journal of Molecular Sciences 16(11): 26291-26302



The Notch signaling pathway orchestrates cell fate by either inducing cell differentiation or maintaining cells in an undifferentiated state. This study aims to evaluate Notch expression and function in normal human keratinocytes. Notch1 is expressed in all epidermal layers, though to a different degree of intensity, with a dramatic decrease during ageing. Notch1 intracellular domain (N1ICD) levels are decreased during transit from keratinocyte stem cells (KSC) to transit amplifying (TA) cells, mimicking survivin expression in samples from donors of all ages. Calcium markedly reduces N1ICD levels in keratinocytes. N1ICD overexpression induces the up-regulation of survivin and the down-regulation of keratin 10 and involucrin, while increasing the S phase of the cell cycle. On the other hand, Notch1 inhibition (DAPT) dose-dependently decreases survivin, stimulates differentiation, and reduces keratinocyte proliferation in samples from donors of all ages. Silencing Notch downgrades survivin and increases keratin 10. In addition, Notch1 inhibition decreases survivin levels and proliferation both in KSC and TA cells. Finally, while survivin overexpression decreases keratinocyte differentiation and increases N1ICD expression both in KSC and TA cells, silencing survivin results in N1ICD down-regulation and an increase in differentiation markers. These results suggest that the Notch1/survivin crosstalk contributes to the maintenance of stemness in human keratinocytes.

(PDF emailed within 0-6 h: $19.90)

Accession: 058427973

Download citation: RISBibTeXText

PMID: 26540052

DOI: 10.3390/ijms161125948


Related references

Transgenic expression of survivin in keratinocytes counteracts UVB-induced apoptosis and cooperates with loss of p53. Journal of Clinical Investigation 108(7): 991-999, 2001

Endogenous survivin modulates survival and proliferation in UVB-treated human keratinocytes. Experimental Dermatology 18(5): 464-471, 2009

Keratin-6 driven ODC expression to hair follicle keratinocytes enhances stemness and tumorigenesis by negatively regulating Notch. Biochemical and Biophysical Research Communications 451(3): 394-401, 2014

Granulocyte and macrophage colony-stimulating factors stimulate proliferation of human keratinocytes. Archives Of Dermatological Research. 289(10): 600-602, 1997

Polysaccharides from Hibiscus sabdariffa flowers stimulate proliferation and differentiation of human keratinocytes. Planta Medica 70(4): 370-373, 2004

12-Hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) does not stimulate proliferation of human neonatal keratinocytes. Journal of Investigative Dermatology 92(5): 683-688, 1989

NLK functions to maintain proliferation and stemness of NSCLC and is a target of metformin. Journal of Hematology & Oncology 8(): 120-120, 2016

Recombinant retroviruses encoding human papillomavirus type 18 E6 and E7 genes stimulate proliferation and delay differentiation of human keratinocytes early after infection. Oncogene 7(4): 619-626, 1992

Typha latifolia L. fruit polysaccharides induce the differentiation and stimulate the proliferation of human keratinocytes in vitro. Journal of Ethnopharmacology 137(1): 352-358, 2011

The human papillomavirus type 16 E5 gene cooperates with the E7 gene to stimulate proliferation of primary cells and increases viral gene expression. Virology 203(1): 73-80, 1994

Human epidermal keratinocytes are induced to secrete interleukin-6 and co-stimulate T lymphocyte proliferation by a CD40-dependent mechanism. European Journal of Immunology 26(6): 1371-1377, 1996

O-fucose monosaccharide of Drosophila Notch has a temperature-sensitive function and cooperates with O-glucose glycan in Notch transport and Notch signaling activation. Journal of Biological Chemistry 290(1): 505-519, 2015

Mesenchymal Stem Cells Isolated From Human Gliomas Increase Proliferation and Maintain Stemness of Glioma Stem Cells Through the IL-6/gp130/STAT3 Pathway. Stem Cells 33(8): 2400-2415, 2016

Notochord-dependent expression of MFH1 and PAX1 cooperates to maintain the proliferation of sclerotome cells during the vertebral column development. Developmental Biology 210(1): 15-29, 1999

Recombinant adenovirus-mediated human telomerase reverse transcriptase gene can stimulate cell proliferation and maintain primitive characteristics in bovine mammary gland epithelial cells. Development, Growth & Differentiation 53(3): 312-322, 2011