p38 MAPK turns hepatocyte growth factor to a death signal that commits ovarian cancer cells to chemotherapy-induced apoptosis

Nadia Coltella, Andrea Rasola, Elisa Nano, Chiara Bardella, Michela Fassetta, Nicoletta Filigheddu, Andrea Graziani, Paolo M. Comoglio, Maria Flavia Di Renzo

Research output: Contribution to journalArticle

Abstract

We recently showed that Hepatocyte Growth Factor (HGF), known as a survival factor, unexpectedly enhances apoptosis in human ovarian cancer cells treated with the front-line chemotherapeutics cisplatin (CDDP) and paclitaxel (PTX). Here we demonstrate that this effect depends on the p38 mitogen-activated kinase (MAPK). In fact, p38 MAPK activity is stimulated by HGF and further increased by the combined treatment with HGF and either CDDP or PTX. The expression of a dominant negative form of p38 MAPK abrogates apoptosis elicited by drugs, alone or in combination with HGF. HGF and drugs also activate the ERK1/2 MAPKs, the PI3K/AKT and the AKT substrate mTOR. However, activation of these survival pathways does not hinder the ability of HGF to enhance drug-dependent apoptosis. Altogether data show that p38 MAPK is necessary for HGF sensitization of ovarian cancer cells to low-doses of CDDP and PTX and might be sufficient to overcome activation of survival pathways. Therefore, the p38 MAPK pathway might be a suitable target to improve response to conventional chemotherapy in human ovarian cancer.

Original languageEnglish
Pages (from-to)2981-2990
Number of pages10
JournalInternational Journal of Cancer
Volume118
Issue number12
DOIs
Publication statusPublished - Jun 15 2006

Keywords

  • Apoptosis
  • Cisplatin
  • HGF
  • p38 MAPK
  • Paclitaxel

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'p38 MAPK turns hepatocyte growth factor to a death signal that commits ovarian cancer cells to chemotherapy-induced apoptosis'. Together they form a unique fingerprint.

  • Cite this

    Coltella, N., Rasola, A., Nano, E., Bardella, C., Fassetta, M., Filigheddu, N., Graziani, A., Comoglio, P. M., & Di Renzo, M. F. (2006). p38 MAPK turns hepatocyte growth factor to a death signal that commits ovarian cancer cells to chemotherapy-induced apoptosis. International Journal of Cancer, 118(12), 2981-2990. https://doi.org/10.1002/ijc.21766