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Inducible silencing of protein kinase D3 inhibits secretion of tumor-promoting factors in prostate cancer.

ABSTRACT: Protein kinase D (PKD) acts as a major mediator of several signaling pathways related to cancer development. Aberrant PKD expression and activity have been shown in multiple cancers, and novel PKD inhibitors show promising anticancer activities. Despite these advances, the mechanisms through which PKD contributes to the pathogenesis of cancer remain unknown. Here, we establish a novel role for PKD3, the least studied member of the PKD family, in the regulation of prostate cancer cell growth and motility through modulation of secreted tumor-promoting factors. Using both a stable inducible knockdown cell model and a transient knockdown system using multiple siRNAs, we show that silencing of endogenous PKD3 significantly reduces prostate cancer cell proliferation, migration, and invasion. In addition, conditioned medium from PKD3-knockdown cells exhibits less migratory potential compared with that from control cells. Further analysis indicated that depletion of PKD3 blocks secretion of multiple key tumor-promoting factors including matrix metalloproteinase (MMP)-9, interleukin (IL)-6, IL-8, and GRO? but does not alter mRNA transcript levels for these factors, implying impairment of the secretory pathway. More significantly, inducible depletion of PKD3 in a subcutaneous xenograft model suppresses tumor growth and decreases levels of intratumoral GRO? in mice. These data validate PKD3 as a promising therapeutic target in prostate cancer and shed light on the role of secreted tumor-promoting factors in prostate cancer progression.

SUBMITTER: LaValle CR

PROVIDER: S-EPMC3392457 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Inducible silencing of protein kinase D3 inhibits secretion of tumor-promoting factors in prostate cancer.

LaValle Courtney R CR Zhang Liyong L Xu Shuping S Eiseman Julie L JL Wang Q Jane QJ

Molecular cancer therapeutics 20120424 7

Protein kinase D (PKD) acts as a major mediator of several signaling pathways related to cancer development. Aberrant PKD expression and activity have been shown in multiple cancers, and novel PKD inhibitors show promising anticancer activities. Despite these advances, the mechanisms through which PKD contributes to the pathogenesis of cancer remain unknown. Here, we establish a novel role for PKD3, the least studied member of the PKD family, in the regulation of prostate cancer cell growth and ...[more]

PMID: 22532599

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Inducible silencing of protein kinase D3 inhibits secretion of tumor-promoting factors in prostate cancer.

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Inducible silencing of protein kinase D3 inhibits secretion of tumor-promoting factors in prostate cancer.

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