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Slug/SNAI2 regulates cell proliferation and invasiveness of metastatic prostate cancer cell lines

  • Research Article
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Tumor Biology

Abstract

Many metastatic cancers recapitulate the epithelial-to-mesenchymal transition (EMT) resulting in enhanced cell motility and invasiveness. The EMT is regulated by several transcription factors, including the zinc finger protein SNAI2, also named Slug, which appears to exert additional functions during development and cancer progression. We have studied the function of SNAI2 in prostate cancer cells. Quantitative RT-PCR analysis showed strong SNAI2 expression particularly in the PC-3 and PC3-16 prostate carcinoma cell lines. Knockdown of SNAI2 by specific siRNA induced changes in EMT markers and inhibited invasion of both cell lines into a matrigel matrix. SNAI2 siRNA-treated cells did not tolerate detachment from the culture plates, likely at least in part due to downregulation of integrin α6β4. SNAI2 knockdown disturbed the microtubular and actin cytoskeletons, especially severely in PC-3 cells, resulting in grossly enlarged, flattened, and sometimes multinuclear cells. Knockdown also decreased cell proliferation, with a prominent G0/G1 arrest in PC3-16. Together, our data imply that SNAI2 exerts strong effects on the cytoskeleton and adhesion of those prostate cancer cells that express it and is necessary for their proliferation and invasiveness.

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Acknowledgments

We thank Christiane Hader and Dr. Parvaneh Nikpour for valuable assistance in several experiments and helpful suggestions.

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Authors and Affiliations

  1. Department of Genetics, Faculty of Basic Sciences, Tarbiat Modares University, Tehran, Iran

    Modjtaba Emadi Baygi

  2. Department of Biochemistry, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran

    Zahra-Soheila Soheili & Abdolkhaleg Deezagi

  3. Interfaculty Institute of Biochemistry, Eberhard Karls University, Tübingen, Germany

    Frank Essmann

  4. Institute of Pathology, Heinrich Heine University, Moorenstrasse 5, 40225, Düsseldorf, Germany

    Rainer Engers

  5. Department of Urology, Heinrich Heine University, P. O. Box 40225, Düsseldorf, Germany

    Wolfgang Goering & Wolfgang A. Schulz

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  1. Modjtaba Emadi Baygi
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  2. Zahra-Soheila Soheili
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  3. Frank Essmann
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  4. Abdolkhaleg Deezagi
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  5. Rainer Engers
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  7. Wolfgang A. Schulz
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Correspondence to Wolfgang A. Schulz.

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Supplementary Table 1

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Supplementary 1

DAPI staining of attached or floating PC-3 or PC3-16 cells after treatment with the indicated siRNAs. In these representative figures, no apoptotic nuclei are visible except one marked by an arrow. In particular, cells centrifuged down from the supernatant onto microscope slides appear clumpy, but not apoptotic. (GIF 2252 kb)

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Emadi Baygi, M., Soheili, ZS., Essmann, F. et al. Slug/SNAI2 regulates cell proliferation and invasiveness of metastatic prostate cancer cell lines. Tumor Biol. 31, 297–307 (2010). https://doi.org/10.1007/s13277-010-0037-5

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  • DOI: https://doi.org/10.1007/s13277-010-0037-5

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