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

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

Triple Negative Breast Neoplasms
Protein Kinases
Biomarkers
Breast Neoplasms
Heterografts
Messenger RNA
Therapeutics
Survival
Protein-Serine-Threonine Kinases
MCF-7 Cells
Protein Kinase Inhibitors
Small Interfering RNA
Estrogens
Pharmacology
Neoplasm Metastasis
Cell Line
Growth

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., ... 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

PKD1 is a potential biomarker and therapeutic target in triplenegative breast cancer. / Spasojevic, Caroline; Marangoni, Elisabetta; Vacher, Sophie; Assayag, Franck; Meseure, Didier; Château-Joubert, Sophie; Humbert, Martine; Doldur, Manale; Ricort, Jean Marc; Auclair, Christian; Regairaz, Marie; Bièche, Ivan.

In: Oncotarget, Vol. 9, No. 33, 01.05.2018, p. 23208-23219.

Research output: Contribution to journalArticle

Spasojevic, C, Marangoni, E, Vacher, S, Assayag, F, Meseure, D, Château-Joubert, S, Humbert, M, Doldur, M, Ricort, JM, Auclair, C, Regairaz, M & Bièche, I 2018, 'PKD1 is a potential biomarker and therapeutic target in triplenegative breast cancer', Oncotarget, vol. 9, no. 33, pp. 23208-23219. https://doi.org/10.18632/oncotarget.25292
Spasojevic C, Marangoni E, Vacher S, Assayag F, Meseure D, Château-Joubert S et al. PKD1 is a potential biomarker and therapeutic target in triplenegative breast cancer. Oncotarget. 2018 May 1;9(33):23208-23219. https://doi.org/10.18632/oncotarget.25292
Spasojevic, Caroline ; Marangoni, Elisabetta ; Vacher, Sophie ; Assayag, Franck ; Meseure, Didier ; Château-Joubert, Sophie ; Humbert, Martine ; Doldur, Manale ; Ricort, Jean Marc ; Auclair, Christian ; Regairaz, Marie ; Bièche, Ivan. / PKD1 is a potential biomarker and therapeutic target in triplenegative breast cancer. In: Oncotarget. 2018 ; Vol. 9, No. 33. pp. 23208-23219.
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