Fhit delocalizes Annexin A4 from plasma membrane to cytosol and sensitizes lung cancer cells to paclitaxel

Eugenio Gaudio, Francesco Paduano, Riccardo Spizzo, Apollinaire Ngankeu, Nicola Zanesi, Marco Gaspari, Francesco Ortuso, Francesca Lovat, Jonathan Rock, Grace A. Hill, Mohamed Kaou, Giovanni Cuda, Rami I. Aqeilan, Stefano Alcaro, Carlo M. Croce, Francesco Trapasso

Research output: Contribution to journalArticlepeer-review

Abstract

Fhit protein is lost or reduced in a large fraction of human tumors, and its restoration triggers apoptosis and suppresses tumor formation or progression in preclinical models. Here, we describe the identification of candidate Fhit-interacting proteins with cytosolic and plasma membrane localization. Among these, Annexin 4 (ANXA4) was validated by co-immunoprecipitation and confocal microscopy as a partner of this novel Fhit protein complex. Here we report that overexpression of Fhit prevents Annexin A4 translocation from cytosol to plasma membrane in A549 lung cancer cells treated with paclitaxel. Moreover, paclitaxel administration in combination with AdFHIT acts synergistically to increase the apoptotic rate of tumor cells both in vitro and in vivo experiments.

Original languageEnglish
Article numbere78610
JournalPLoS One
Volume8
Issue number11
DOIs
Publication statusPublished - Nov 6 2013

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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