Protein kinase D2 and 3 promote prostate cancer cell bone metastasis by positively regulating Runx2 in a MEK/ERK1/2-dependent manner.

Journal article

Adhiraj Roy, S. Prasad, Yuzhou Chen, Ya-Ling Chao, Yu Liu, Jinjun Zhao, Q. Wang
American Journal of Pathology, 2023

Cite

APA Click to copy
Roy, A., Prasad, S., Chen, Y., Chao, Y.-L., Liu, Y., Zhao, J., & Wang, Q. (2023). Protein kinase D2 and 3 promote prostate cancer cell bone metastasis by positively regulating Runx2 in a MEK/ERK1/2-dependent manner. American Journal of Pathology.

Chicago/Turabian Click to copy
Roy, Adhiraj, S. Prasad, Yuzhou Chen, Ya-Ling Chao, Yu Liu, Jinjun Zhao, and Q. Wang. “Protein Kinase D2 and 3 Promote Prostate Cancer Cell Bone Metastasis by Positively Regulating Runx2 in a MEK/ERK1/2-Dependent Manner.” American Journal of Pathology (2023).

MLA Click to copy
Roy, Adhiraj, et al. “Protein Kinase D2 and 3 Promote Prostate Cancer Cell Bone Metastasis by Positively Regulating Runx2 in a MEK/ERK1/2-Dependent Manner.” American Journal of Pathology, 2023.

BibTeX Click to copy

@article{adhiraj2023a,
  title = {Protein kinase D2 and 3 promote prostate cancer cell bone metastasis by positively regulating Runx2 in a MEK/ERK1/2-dependent manner.},
  year = {2023},
  journal = {American Journal of Pathology},
  author = {Roy, Adhiraj and Prasad, S. and Chen, Yuzhou and Chao, Ya-Ling and Liu, Yu and Zhao, Jinjun and Wang, Q.}
}

Abstract

Advanced stage prostate tumors frequently metastasize to the bone, which is the main cause of death. The protein kinase D (PKD) family has been implicated in prostate cancer development; however, its role in prostate cancer metastasis has not been investigated. This study examined the contribution of PKD, particularly PKD2 and 3 (PKD2/3), to the metastatic potential of prostate cancer cells and the effect of PKD inhibition on prostate cancer bone metastasis in vivo. The data showed that depletion of PKD2/3 by siRNAs or inhibition by a PKD inhibitor CRT0066101 in AR-positive and -negative castration-resistant prostate cancer cells potently inhibited colony formation and cell migration. Furthermore, depletion or inhibition of PKD2/3 significantly blocked tumor cell invasion and suppressed the expression of genes related to bone metastasis in the highly invasive PC3-ML cells. The reduced invasive activity resulting from PKD2/3 depletion was in part mediated by the transcription factor Runx2, as its silencing decreased PKD2/3-mediated metastatic gene expression through the MEK/ERK1/2 signaling axis. Furthermore, inhibition of PKD by CRT0066101 potently decreased the frequency of bone micrometastases in a mouse model of bone metastasis based on intracardiac injection of PC3-ML cells. These results indicate that PKD2/3 play an important role in the bone metastasis of prostate cancer cells, and their inhibition may be beneficial for the treatment of advanced stages of prostate cancer.