PKD1 is a potential biomarker and therapeutic target in triple-negative breast cancer.

PKD1 is a potential biomarker and therapeutic target in triple-negative breast cancer. Oncotarget. 2018 May 01;9(33):23208-23219 Authors: Spasojevic C, Marangoni E, Vacher S, Assayag F, Meseure D, Château-Joubert S, Humbert M, Karam M, Ricort JM, Auclair C, Regairaz M, Bièche I 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 ERα+ tamoxifen-resistant breast tumors and PKD1 overexpression confers estrogen independence to ERα+ 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 prog...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research