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Plakophilin 1-deficient cells upregulate SPOCK1: implications for prostate cancer progression

  • Research Article
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Tumor Biology

Abstract

Plakophilin (PKP) 1 is frequently downregulated in prostate cancer and therefore may play a tumor-suppressive role. In the present study, we stably knocked down PKP1 in the non-neoplastic, prostatic BPH-1 cell line. In the PKP1-deficient cells, the expression of keratin 14 was lost, and the apoptosis rate was significantly reduced indicating that the cells acquired new biological capabilities. Moreover, we analyzed the gene expression profile of the PKP1-deficient BPH-1 cells. Among the genes that were significantly altered upon PKP1 knockdown, we noticed several extracellular matrix (ECM)-related genes and identified sparc/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1/testican-1) as a gene of interest. SPOCK1 is a component of the ECM and belongs to a matricellular protein family named secreted protein, acidic, cysteine-rich (SPARC). The role of SPOCK1 in prostate cancer has not been clearly elucidated. We analyzed SPOCK1 mRNA expression levels in different cancer databases and characterized its expression in 136 prostatic adenocarcinomas by immunohistochemistry and western blot. SPOCK1 revealed a cytoplasmic localization in the glandular epithelium of the prostate and showed a significant upregulation of mRNA and protein in prostate tumor samples. Our findings support the hypothesis that PKP1 may have a tumor-suppressive function and suggest an important role of SPOCK1 in prostate tumor progression. Collectively, altered expression of PKP1 and SPOCK1 appears to be a frequent and critical event in prostate cancer.

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Acknowledgments

This study was funded by grants from the German Cancer Aid (109248) and the “Deutsche Forschungsgemeinschaft” (HO 2455/3-1). Cheng Yang obtained a fellowship from the Chinese Scholarship Council (CSC). We thank the microarray unit of the DKFZ Genomics and Proteomics Core Facility for providing the Illumina Whole-Genome Expression Beadchips and related services.

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Authors and Affiliations

  1. Division of Vascular Oncology and Metastasis, German Cancer Research Center, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Cheng Yang, Regina Fischer-Kešo, Tanja Schlechter & Ilse Hofmann

  2. Department of Vascular Biology and Tumor Angiogenesis (CBTM), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    Cheng Yang, Regina Fischer-Kešo, Tanja Schlechter & Ilse Hofmann

  3. Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany

    Philipp Ströbel

  4. Institute of Pathology, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany

    Alexander Marx

  5. Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China

    Cheng Yang

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  1. Cheng Yang
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  2. Regina Fischer-Kešo
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Correspondence to Ilse Hofmann.

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Yang, C., Fischer-Kešo, R., Schlechter, T. et al. Plakophilin 1-deficient cells upregulate SPOCK1: implications for prostate cancer progression. Tumor Biol. 36, 9567–9577 (2015). https://doi.org/10.1007/s13277-015-3628-3

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