PKCν is an anti-apoptotic kinase that predicts poor prognosis in breast and lung cancer

Udi Zurgil, Assaf Ben-Ari, Noa Rotem-Dai, Galia Karp, Ella Krasnitsky, Sigal A. Frost, Etta Livneh

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The successful treatment of cancer in a disseminated stage using chemotherapy is limited by the occurrence of drug resistance, often mediated by anti-apoptotic mechanisms. Thus the challenge is to pinpoint the underlying key factors and to develop therapies for their direct targeting. Protein kinase C (PKC) enzymes are promising candidates, as some PKCs were shown to be involved in regulation of apoptosis. Our studies and others have shown that PKCν is an anti-apoptotic kinase, able to confer protection on tumour cells against stress and chemotherapy. We have demonstrated that PKCν shuttles between the cytoplasm and the nucleus and that upon DNA damage is tethered at the nuclear membrane. The C1b domain mediates translocation of PKCν to the nuclear envelope and, similar to the full-length protein, could also confer protection against cell death. Furthermore, its localization in cell and nuclear membranes in breast cancer biopsies of neoadjuvant-treated breast cancer patients was an indicator for poor survival and a predictor for the effectiveness of treatment. PKCν is also a novel biomarker for poor prognosis in non-small-cell lung cancer (NSCLC). Thus PKCν presents a potential target for therapy where inhibition of its activity and/or translocation to membranes could interfere with the resistance to chemotherapy.

Original languageEnglish
Pages (from-to)1519-1523
Number of pages5
JournalBiochemical Society Transactions
Volume42
Issue number6
DOIs
StatePublished - 1 Dec 2014

Keywords

  • Apoptosis
  • Breast cancer
  • Neoadjuvant
  • Non-small-cell lung cancer (NSCLC)
  • Patient survival
  • Predicting response to therapy
  • Prognostic biomarker
  • Protein kinase Cν (PKCν)

ASJC Scopus subject areas

  • Biochemistry

Fingerprint

Dive into the research topics of 'PKCν is an anti-apoptotic kinase that predicts poor prognosis in breast and lung cancer'. Together they form a unique fingerprint.

Cite this