PKD1 is a potential biomarker and therapeutic target in triplenegative breast cancer

Caroline Spasojevic, Elisabetta Marangoni, Sophie Vacher, Franck Assayag, Didier Meseure, Sophie Château-Joubert, Martine Humbert, Manale Doldur, Jean Marc Ricort, Christian Auclair, Marie Regairaz, Ivan Bièche

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Protein Kinase D1 (PKD1) is a serine/threonine kinase encoded by the PRKD1 gene. PKD1 has been previously shown to be a prognostic factor in ERa+ tamoxifenresistant breast tumors and PKD1 overexpression confers estrogen independence to ERa+ MCF7 cells. In the present study, our goal was to determine whether PKD1 is a prognostic factor and/or a relevant therapeutic target in breast cancer. We analyzed PRKD1 mRNA levels in 527 primary breast tumors. We found that high PRKD1 mRNA levels were significantly and independently associated with a low metastasis-free survival in the whole breast cancer population and in the triple-negative breast cancer (TNBC) subtype specifically. High PRKD1 mRNA levels were also associated with a low overall survival in TNBC. We identified novel PKD1 inhibitors and assessed their antitumor activity in vitro in TNBC cell lines and in vivo in a TNBC patient-derived xenograft (PDX) model. Pharmacological inhibition and siRNA-mediated depletion of PKD1 reduced colony formation in MDA-MB-436 TNBC cells. PKD1 inhibition also reduced tumor growth in vivo in a TNBC PDX model. Together, these results establish PKD1 as a poor prognostic factor and a potential therapeutic target in TNBC.

Original languageEnglish
Pages (from-to)23208-23219
Number of pages12
JournalOncotarget
Volume9
Issue number33
DOIs
Publication statusPublished - 1 May 2018

    Fingerprint

Keywords

  • PKC
  • PKD
  • Protein kinase D1
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Oncology

Cite this

Spasojevic, C., Marangoni, E., Vacher, S., Assayag, F., Meseure, D., Château-Joubert, S., Humbert, M., Doldur, M., Ricort, J. M., Auclair, C., Regairaz, M., & Bièche, I. (2018). PKD1 is a potential biomarker and therapeutic target in triplenegative breast cancer. Oncotarget, 9(33), 23208-23219. https://doi.org/10.18632/oncotarget.25292