%0 Journal Article %1 GALI2024108958 %A Gali, Alexia %A Bijnsdorp, Irene V. %A Piersma, Sander R. %A Pham, Thang V. %A Gutiérrez-Galindo, Elena %A Kühnel, Fiona %A Tsolakos, Nikos %A Jimenez, Connie R. %A Hausser, Angelika %A Alexopoulos, Leonidas G. %D 2024 %J iScience %K 2024 hausser izi %P 108958 %R https://doi.org/10.1016/j.isci.2024.108958 %T Protein Kinase D drives the secretion of invasion mediators in triple-negative breast cancer cell lines %U https://www.sciencedirect.com/science/article/pii/S2589004224001792 %X Summary 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.

@article{GALI2024108958, abstract = {Summary 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.}, added-at = {2024-01-18T11:15:16.000+0100}, author = {Gali, Alexia and Bijnsdorp, Irene V. and Piersma, Sander R. and Pham, Thang V. and Gutiérrez-Galindo, Elena and Kühnel, Fiona and Tsolakos, Nikos and Jimenez, Connie R. and Hausser, Angelika and Alexopoulos, Leonidas G.}, biburl = {https://puma.ub.uni-stuttgart.de/bibtex/2aabe6d0bc48c8228a8c9ae0e05a0398e/fabian}, description = {Protein Kinase D drives the secretion of invasion mediators in triple-negative breast cancer cell lines - ScienceDirect}, doi = {https://doi.org/10.1016/j.isci.2024.108958}, interhash = {7853db687d965c4311cb3e0da637be63}, intrahash = {aabe6d0bc48c8228a8c9ae0e05a0398e}, issn = {2589-0042}, journal = {iScience}, keywords = {2024 hausser izi}, pages = 108958, timestamp = {2024-01-18T11:15:16.000+0100}, title = {Protein Kinase D drives the secretion of invasion mediators in triple-negative breast cancer cell lines}, url = {https://www.sciencedirect.com/science/article/pii/S2589004224001792}, year = 2024 }