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PKCϵ Is an Essential Mediator of Prostate Cancer Bone Metastasis
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| Zeitschriftentitel: | Molecular Cancer Research |
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| Personen und Körperschaften: | , , , , |
| In: | Molecular Cancer Research, 13, 2015, 9, S. 1336-1346 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
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| Schlagwörter: |
| Zusammenfassung: | <jats:title>Abstract</jats:title> <jats:p>The bone is a preferred site for metastatic homing of prostate cancer cells. Once prostate cancer patients develop skeletal metastases, they eventually succumb to the disease; therefore, it is imperative to identify key molecular drivers of this process. This study examines the involvement of protein kinase C epsilon (PKCϵ), an oncogenic protein that is abnormally overexpressed in human tumor specimens and cell lines, on prostate cancer cell bone metastasis. PC3-ML cells, a highly invasive prostate cancer PC3 derivative with bone metastatic colonization properties, failed to induce skeletal metastatic foci upon inoculation into nude mice when PKCϵ expression was silenced using shRNA. Interestingly, while PKCϵ depletion had only marginal effects on the proliferative, adhesive, and migratory capacities of PC3-ML cells in vitro or in the growth of xenografts upon s.c. inoculation, it caused a significant reduction in cell invasiveness. Notably, PKCϵ was required for transendothelial cell migration (TEM) as well as for the growth of PC3-ML cells in a bone biomimetic environment. At a mechanistic level, PKCϵ depletion abrogates the expression of IL1β, a cytokine implicated in skeletal metastasis. Taken together, PKCϵ is a key factor for driving the formation of bone metastasis by prostate cancer cells and is a potential therapeutic target for advanced stages of the disease.</jats:p> <jats:p>Implications: This study uncovers an important new function of PKCϵ in the dissemination of cancer cells to the bone; thus, highlighting the promising potential of this oncogenic kinase as a therapeutic target for skeletal metastasis. Mol Cancer Res; 13(9); 1336–46. ©2015 AACR.</jats:p> |
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| Umfang: | 1336-1346 |
| ISSN: |
1557-3125
1541-7786 |
| DOI: | 10.1158/1541-7786.mcr-15-0111 |