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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

SET/I2PP2A overexpression induces phenotypic, molecular, and metabolic alterations in an oral keratinocyte cell line

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Author(s):
Sobral, Lays M. [1, 2] ; Coletta, Ricardo D. [3] ; Alberici, Luciane C. [4] ; Curti, Carlos [4] ; Leopoldino, Andreia M. [1, 2]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Sch Med Ribeirao Preto, Ctr Cell Based Therapy, CEPID FAPESP, Ribeirao Preto, SP - Brazil
[3] Univ Estadual Campinas, Piracicaba Dent Sch, Dept Oral Diag, Piracicaba, SP - Brazil
[4] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, Ribeirao Preto, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: FEBS Journal; v. 284, n. 17, p. 2774-2785, SEP 2017.
Web of Science Citations: 3
Abstract

The multifunctional SET/I2PP2A protein is known to be overexpressed in head and neck squamous cell carcinoma. However, SET has been reported to have apparently conflicting roles in promoting cancer cell survival under oxidative stress conditions and preventing invasion and metastasis, complicating efforts to understand the contribution of SET to carcinogenesis. In the present study, we overexpressed SETin a spontaneously immortalized oral keratinocyte cell line (NOK-SI SET) and demonstrated that SET upregulation alone was sufficient to transform cells. In comparison with NOK-SI cells, NOK-SI SET cells demonstrated increased levels of phosphorylated Akt, c-Myc and inactive/phosphorylated Rb, together with decreased total Rb protein levels. In addition, NOK-SI SET cells presented the following: (a) a spindle-cell shape morphology compared with the polygonal morphology of NOK-SI cells; (b) loss of mesenchymal stem cell markers CD44 and CD73, and epithelial cell markers CD71 and integrin a6/b4; (c) the ability to form xenograft tumors in nude mice; and (d) increased mitochondrial respiration accompanied by decreased ROSlevels. Overall, our results show that SEToverexpression promotes morphological and oncogenic cell transformation of an oral keratinocyte cell. (AU)

FAPESP's process: 10/18544-9 - Profile analysis of SET-associated miRNAs and its effects on proliferation, invasion and migration in an oral squamous cell carcinoma model - in vivo and in vitro
Grantee:Lays Martin Sobral
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 13/10898-4 - Study of the molecular mechanisms by protein SET with impact on tumorigenesis and progression of oral cancer
Grantee:Carlos Curti
Support type: Regular Research Grants
FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
Grantee:Dimas Tadeu Covas
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC