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Long glucocorticoid-induced leucine zipper regulates human thyroid cancer cell proliferation

TitoloLong glucocorticoid-induced leucine zipper regulates human thyroid cancer cell proliferation
Tipo di pubblicazioneArticolo su Rivista peer-reviewed
Anno di Pubblicazione2018
AutoriAyroldi, Emira, Petrillo Maria Grazia, Marchetti Maria Cristina, Cannarile Lorenza, Ronchetti Simona, Ricci Erika, Cari Luigi, Avenia Nicola, Moretti Sonia, Puxeddu Efisio, and Riccardi Carlo
RivistaCell Death and Disease
Volume9
Type of ArticleArticle
ISSN20414889
Parole chiave1, 3 butadiene, 3 dicyanobutadiene, 4 bis(2 aminophenylthio) 2, 4 diamino 1, animal cell, animal experiment, animal model, antiproliferative activity, article, B Raf kinase, Biological, biological model, Butadienes, cancer growth, cell differentiation, Cell Line, cell proliferation, controlled study, cyclic AMP dependent protein kinase, Cyclic AMP Response Element-Binding Protein, cyclic AMP responsive element binding protein, Cyclic AMP-Dependent Protein Kinases, drug effect, enzyme activation, Female, gene expression regulation, gene mutation, gene silencing, Genetic, genetics, human, human cell, Humans, hybrid protein, leucine zipper protein, long glucocorticoid induced leucine zipper, metabolism, mitogen activated protein kinase, mitogen activated protein kinase inhibitor, Mitogen-Activated Protein Kinases, Models, mouse, Neoplastic, nitrile, Nitriles, nonhuman, Pathology, Phosphorylation, priority journal, promoter region, Promoter Regions, protein expression, protein function, protein kinase inhibitor, Protein Kinase Inhibitors, protein phosphorylation, Ras association domain family protein 1A, Sorafenib, thyroid cancer, thyroid cancer cell line, Thyroid Neoplasms, thyroid tumor, transcription factor, Transcription Factors, transcription initiation, Transcriptional Activation, TSC22D3 protein, Tumor, tumor cell line, unclassified drug, Up-Regulation, upregulation, Vemurafenib
Abstract

Long glucocorticoid-induced leucine zipper (L-GILZ) has recently been implicated in cancer cell proliferation. Here, we investigated its role in human thyroid cancer cells. L-GILZ protein was highly expressed in well-differentiated cancer cells from thyroid cancer patients and differentiated thyroid cancer cell lines, but poorly expressed in anaplastic tumors. A fusion protein containing L-GILZ, when overexpressed in an L-GILZ-deficient 8505C cell line derived from undifferentiated human thyroid cancer tissue, inhibited cellular proliferation in vitro. In addition, when this protein was injected into nude mice, in which cells from line 8505C had been transplanted, xenograft growth was reduced. Since the mitogen-Activated protein kinase (MAPK) pathway is frequently hyperactivated in thyroid cancer cells as a result of the BRAFV600E or Ras mutation, we sought to further investigate the role of L-GILZ in the MAPK pathway. To this end, we analyzed L-GILZ expression and function in cells treated with MAPK inhibitors. We used 8505C cells, which have the BRAFV600E mutation, or the CAL-62 cell line, which harbors a Ras mutation. The cells were treated with the BRAF-specific drug vemurafenib (PLX4032) or the MEK1/2 inhibitor, U0126, respectively. Treatment with these agents inhibited MAPK activation, reduced cell proliferation, and upregulated L-GILZ expression. L-GILZ silencing reversed the antiproliferative activity of the MAPK inhibitors, consistent with an antiproliferative role. Treatment with MAPK inhibitors led to the phosphorylation of the cAMP/response element-binding protein (CREB), and active CREB bound to the L-GILZ promoter, contributing to its transcription. We suggest that the CREB signaling pathway, frequently deregulated in thyroid tumors, is involved in L-GILZ upregulation and that L-GILZ regulates thyroid cancer cell proliferation, which may have potential in cancer treatment. © 2018 The Author(s).

Note

Cited by: 17; All Open Access, Gold Open Access, Green Open Access

URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85042356962&doi=10.1038%2fs41419-018-0346-y&partnerID=40&md5=a398766fa70872aa4532f6d40e50f5f5
DOI10.1038/s41419-018-0346-y
Citation KeyAyroldi2018
PubMed ID29467389