Protein kinase D drives the secretion of invasion mediators in triple-negative breast cancer cell lines

• Published in: iScience 2024-02, Vol.27 (2), p.108958-108958, Article 108958
• Main Authors: Gali, Alexia, Bijnsdorp, Irene V., Piersma, Sander R., Pham, Thang V., Gutiérrez-Galindo, Elena, Kühnel, Fiona, Tsolakos, Nikos, Jimenez, Connie R., Hausser, Angelika, Alexopoulos, Leonidas G.
• Format: Article
• Language: English
• Subjects: Cancer; Cell biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.108958

The protein kinase D (PKD) family members regulate the fission of cargo vesicles at the Golgi complex and play a pro-oncogenic role in triple-negative breast cancer (TNBC). Whether PKD facilitates the secretion of tumor-promoting factors in TNBC, however, is still unknown. Using the pharmacological inhibition of PKD activity and siRNA-mediated depletion of PKD2 and PKD3, we identified the PKD-dependent secretome of the TNBC cell lines MDA-MB-231 and MDA-MB-468. Mass spectrometry-based proteomics and antibody-based assays revealed a significant downregulation of extracellular matrix related proteins and pro-invasive factors such as LIF, MMP-1, MMP-13, IL-11, M-CSF and GM-CSF in PKD-perturbed cells. Notably, secretion of these proteins in MDA-MB-231 cells was predominantly controlled by PKD2 and enhanced spheroid invasion. Consistently, PKD-dependent secretion of pro-invasive factors was more pronounced in metastatic TNBC cell lines. Our study thus uncovers a novel role of PKD2 in releasing a pro-invasive secretome. [Display omitted] •PKD2/3 signaling is important for the composition of the TNBC cell secretome•PKD2 regulates the secretion of six invasion-promoting proteins in TNBC cells•The PKD2-regulated secretome in TNBC has invasion-promoting properties in vitro•PKD2/3 promote the secretion of TNBC invasion mediators mainly in metastatic cell lines Cell biology; Cancer