Premium
SET /I2 PP 2A overexpression induces phenotypic, molecular, and metabolic alterations in an oral keratinocyte cell line
Author(s) -
Sobral Lays M.,
Coletta Ricardo D.,
Alberici Luciane C.,
Curti Carlos,
Leopoldino Andréia M.
Publication year - 2017
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14148
Subject(s) - cd44 , cell , downregulation and upregulation , keratinocyte , cell culture , carcinogenesis , cancer research , microbiology and biotechnology , stem cell , biology , chemistry , cell growth , cancer , biochemistry , genetics , gene
The multifunctional SET /I2 PP 2A 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 SET in 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 CD 44 and CD 73, and epithelial cell markers CD 71 and integrin α6/β4; (c) the ability to form xenograft tumors in nude mice; and (d) increased mitochondrial respiration accompanied by decreased ROS levels. Overall, our results show that SET overexpression promotes morphological and oncogenic cell transformation of an oral keratinocyte cell.