Joint research article published in iScience

18. Januar 2024

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

Gali, A., Bijnsdorp, I. V., Piersma, S. R., Pham, T. V., Gutiérrez-Galindo, E., Kühnel, F., Tsolakos, N., Jimenez, C. R., Hausser, A. & Alexopoulos, L. G.

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 secretion of tumor-promoting factors in TNBC, however, is still unknown. Using 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.

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