Stable and high expression of Galectin-8 tightly controls metastatic progression of prostate cancer
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Lucas Daniel Gentilini1, Felipe Martín Jaworski1,*, Carolina Tiraboschi1,*, Ignacio González Pérez1, Monica Lidia Kotler2, Anne Chauchereau3, Diego Jose Laderach1,4 and Daniel Compagno1
1Molecular and Functional Glyco-Oncology Laboratory, IQUIBICEN-CONICET, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina
2Laboratorio de Disfunción Celular en Enfermedades Neurodegenerativas y Nanomedicina, IQUIBICEN-CONICET, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina
3Institut Gustave Roussy-INSERM U981, Villejuif, France
4Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Argentina
*These authors have contributed equally to this work
Keywords: prostate cancer, galectins, anoikis resistance, metastasis, tumour microenvironment
Received: October 02, 2016 Accepted: April 23, 2017 Published: May 18, 2017
Two decades ago, Galectin-8 was described as a prostate carcinoma biomarker since it is only expressed in the neoplastic prostate, but not in the healthy tissue. To date, no biological function has been attributed to Galectin-8 that could explain this differential expression. In this study we silenced Galectin-8 in two human prostate cancer cell lines, PC3 and IGR-CaP1, and designed a pre-clinical experimental model that allows monitoring the pathology from its early steps to the long-term metastatic stages. We show for the first time that the natural and conserved expression of Gal-8 in tumour cells is responsible for the metastatic evolution of prostate cancer. In fact, Gal-8 controls the rearrangement of the cytoskeleton and E-Cadherin expression, with a major impact on anoikis and homotypic aggregation of tumour cells, both being essential processes for the survival of circulating tumour cells during metastasis. While localized prostate cancer can be cured, metastatic and advanced disease remains a significant therapeutic challenge, urging for the identification of prognostic markers of the metastatic process. Collectively, our results highlight Galectin-8 as a potential target for anti-metastatic therapy against prostate cancer.
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