AI Article Synopsis

  • The PKD family of proteins is important in regulating the fission of cargo vesicles in the Golgi complex and has been linked to promoting tumor growth in triple-negative breast cancer (TNBC).
  • Research investigated the role of PKD in the secretion of factors that promote tumors in TNBC by using drug inhibitors and RNA techniques to deplete specific PKD variants.
  • Findings revealed that inhibiting PKD activity significantly reduced the release of proteins associated with cell invasiveness and extracellular matrix organization, particularly showcasing the crucial role of PKD2 in this process.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10844833PMC
http://dx.doi.org/10.1016/j.isci.2024.108958DOI Listing

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