TY - JOUR
T1 - Protein kinase D drives the secretion of invasion mediators in triple-negative breast cancer cell lines
AU - Gali, Alexia
AU - Bijnsdorp, Irene V.
AU - Piersma, Sander R.
AU - Pham, Thang V.
AU - Gutiérrez-Galindo, Elena
AU - Kühnel, Fiona
AU - Tsolakos, Nikos
AU - Jimenez, Connie R.
AU - Hausser, Angelika
AU - Alexopoulos, Leonidas G.
N1 - Publisher Copyright: © 2024
PY - 2024/2/16
Y1 - 2024/2/16
N2 - 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.
AB - 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.
KW - Cancer
KW - Cell biology
UR - http://www.scopus.com/inward/record.url?scp=85183485806&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2024.108958
DO - 10.1016/j.isci.2024.108958
M3 - Article
C2 - 38323010
SN - 2589-0042
VL - 27
JO - iScience
JF - iScience
IS - 2
M1 - 108958
ER -