TRAP1 regulates cell cycle and apoptosis in thyroid carcinoma cells

Giuseppe Palladino, Tiziana Notarangelo, Giuseppe Pannone, Annamaria Piscazzi, Olga Lamacchia, Lorenza Sisinni, Girolamo Spagnoletti, Paolo Toti, Angela Santoro, Giovanni Storto, Pantaleo Bufo, Mauro Cignarelli, Franca Esposito, Matteo Landriscina

Research output: Contribution to journalArticle

Abstract

Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a heat shock protein 90 (HSP90) molecular chaperone upregulated in several human malignancies and involved in protection from apoptosis and drug resistance, cell cycle progression, cell metabolism and quality control of specific client proteins. TRAP1 role in thyroid carcinoma (TC), still unaddressed at present, was investigated by analyzing its expression in a cohort of 86 human TCs and evaluating its involvement in cancer cell survival and proliferation in vitro. Indeed, TRAP1 levels progressively increased from normal peritumoral thyroid gland, to papillary TCs (PTCs), follicular variants of PTCs (FV-PTCs) and poorly differentiated TCs (PDTCs). By contrast, anaplastic thyroid tumors exhibited a dual pattern, the majority being characterized by high TRAP1 levels, while a small subgroup completely negative. Consistently with a potential involvement of TRAP1 in thyroid carcinogenesis, TRAP1 silencing resulted in increased sensitivity to paclitaxel-induced apoptosis, inhibition of cell cycle progression and attenuation of ERK signaling. Noteworthy, the inhibition of TRAP1 ATPase activity by pharmacological agents resulted in attenuation of cell proliferation, inhibition of ERK signaling and reversion of drug resistance. These data suggest that TRAP1 inhibition may be regarded as potential strategy to target specific features of human TCs, i.e., cell proliferation and resistance to apoptosis.

Original languageEnglish
Pages (from-to)699-709
Number of pages11
JournalEndocrine-Related Cancer
Volume23
Issue number9
DOIs
Publication statusPublished - 2016

Keywords

  • Apoptosis
  • Cell cycle
  • HSP990
  • Thyroid carcinoma
  • TRAP1

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

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  • Cite this

    Palladino, G., Notarangelo, T., Pannone, G., Piscazzi, A., Lamacchia, O., Sisinni, L., Spagnoletti, G., Toti, P., Santoro, A., Storto, G., Bufo, P., Cignarelli, M., Esposito, F., & Landriscina, M. (2016). TRAP1 regulates cell cycle and apoptosis in thyroid carcinoma cells. Endocrine-Related Cancer, 23(9), 699-709. https://doi.org/10.1530/ERC-16-0063