Fhit Nuclear Import Following EGF Stimulation Sustains Proliferation of Breast Cancer Cells

Francesca Bianchi, Marianna Sasso, Federica Turdo, Giovanni L. Beretta, Patrizia Casalini, Cristina Ghirelli, Lucia Sfondrini, Sylvie Ménard, Elda Tagliabue, Manuela Campiglio

Research output: Contribution to journalArticle

Abstract

The tumor-suppressor protein fragile histidine triad (Fhit) exerts its functions in the cytoplasm, although some reports suggest that it may also act in the nucleus. We previously showed that cytosolic Fhit protein levels in cancer cell lines stimulated to proliferate were reduced by proteasomal degradation. Here, we demonstrate that Fhit is physiologically present in the nucleus of breast cancer cell lines and tissues at a low level and that proliferative stimulation increases nuclear levels. Breast cancer cells expressing the FhitY114F mutant, which do not undergo proteasomal degradation, contained mutated Fhit in the nucleus, while cells treated with a proteasome inhibitor accumulated nuclear Fhit during proliferation. Thus, Fhit nuclear shuttling and proteasome degradation phenomena occur independently. When Fhit was coupled to a nuclear localization sequence, the proliferation rate of the transfected cells increased together with levels of proliferation pathway mediators cyclin D1, phospho-MAPK, and phospho-STAT3. Fhit nuclear translocation upon mitogenic stimulation may represent a new regulatory mechanism that allows rapid restoration of Fhit cytoplasmic levels and promotes the proliferation cascade activated by mitogenic stimulation.

Original languageEnglish
Pages (from-to)2661-2670
Number of pages10
JournalJournal of Cellular Physiology
Volume230
Issue number11
DOIs
Publication statusPublished - Nov 1 2015

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ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Medicine(all)

Cite this

Bianchi, F., Sasso, M., Turdo, F., Beretta, G. L., Casalini, P., Ghirelli, C., Sfondrini, L., Ménard, S., Tagliabue, E., & Campiglio, M. (2015). Fhit Nuclear Import Following EGF Stimulation Sustains Proliferation of Breast Cancer Cells. Journal of Cellular Physiology, 230(11), 2661-2670. https://doi.org/10.1002/jcp.24968