c-Myc modulation: a key role in melanoma drug response

Annalisa Fico, Daniela Alfano, Anna Valentino, Valeria Vasta, Ernesta Cavalcanti, Salvatore Travali, Eduardo J. Patriarca, Emilia Caputo

Research output: Contribution to journalArticlepeer-review

Abstract

Understanding molecular mechanisms involved in melanoma resistance to drugs is a big challenge. Experimental evidences suggested a correlation between mutational status in B-RAF and melanoma cell susceptibility to drugs, such as paclitaxel, doxorubicin and temozolomide, which generate an accumulation of hydrogen peroxide (H2O2) in the cells. We investigated the survival phenotype and the protein level of c-myc, a B-RAF target molecule, in melanoma cells, carrying a different mutational status in B-RAF, upon paclitaxel, doxorubicin and H2O2 treatment. For the first time, we reported c-myc modulation is critical for melanoma drug response. It appeared drug-specific and post-transcriptionally driven through PP2A; in correlation, cell pre-treatment with okadaic acid (OA), a specific PP2A inhibitor, as well as PP2A silencing of melanoma cells, was able to increase melanoma cell drug-sensitivity and c-myc protein level. This is relevant for designing efficacious therapeutic strategies in melanoma.

Original languageEnglish
Pages (from-to)1375-1386
Number of pages12
JournalCancer Biology and Therapy
Volume16
Issue number9
DOIs
Publication statusPublished - Sep 2 2015

Keywords

  • B-RAF mutations
  • c-myc modulation
  • cancer therapy
  • chemotherapy
  • melanoma drug resistance, PP2A activity

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology

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