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Open AccessArticle

Embigin Promotes Prostate Cancer Progression by S100A4-Dependent and-Independent Mechanisms

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Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
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Department of Biochemistry, Faculty of Medicine, Udayana University, Denpasar 80232, Bali, Indonesia
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Faculty of Science and Technology, Division of Molecular Science, Gunma University, Gunma 376-8515, Japan
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Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medicine and Dental Sciences, Niigata 951-8510, Japan
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Department of Biochemistry, Kawasaki Medical School, Okayama 701-0192, Japan
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Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
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Department of Pharmacology, Faculty of Medicine, Udayana University, Denpasar 80232, Bali, Indonesia
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Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
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Author to whom correspondence should be addressed.
Cancers 2018, 10(7), 239; https://doi.org/10.3390/cancers10070239
Received: 4 July 2018 / Revised: 18 July 2018 / Accepted: 19 July 2018 / Published: 23 July 2018
Embigin, a transmembrane glycoprotein belonging to the immunoglobulin superfamily, is involved in prostate and mammary gland development. As embigin’s roles in cancer remain elusive, we studied its biological functions and interaction with extracellular S100A4 in prostate cancer progression. We found by a pull-down assay that embigin is a novel receptor for S100A4, which is one of the vital cancer microenvironment milleu. Binding of extracellular S100A4 to embigin mediates prostate cancer progression by inhibition of AMPK activity, activation of NF-κB, MMP9 and mTORC1 signaling, and inhibition of autophagy, which increase prostate cancer cell motility. We also found that embigin promotes prostate cancer growth, spheroid- and colony-forming ability, and survival upon chemotherapy independently of S100A4. An in vivo growth mouse model confirmed the importance of embigin and its cytoplasmic tail in mediating prostate tumor growth. Moreover, embigin and p21WAF1 can be used to predict survival of prostate cancer patients. Our results demonstrated for the first time that the S100A4-embigin/AMPK/mTORC1/p21WAF1 and NF-κB/MMP9 axis is a vital oncogenic molecular cascade for prostate cancer progression. We proposed that embigin and p21WAF1 could be used as prognostic biomarkers and a strategy to inhibit S100A4-embigin binding could be a therapeutic approach for prostate cancer patients. View Full-Text
Keywords: extracellular S100A4; embigin; AMPK; mTORC1; prostate cancer progression extracellular S100A4; embigin; AMPK; mTORC1; prostate cancer progression
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Ruma, I.M.W.; Kinoshita, R.; Tomonobu, N.; Inoue, Y.; Kondo, E.; Yamauchi, A.; Sato, H.; Sumardika, I.W.; Chen, Y.; Yamamoto, K.-I.; Murata, H.; Toyooka, S.; Nishibori, M.; Sakaguchi, M. Embigin Promotes Prostate Cancer Progression by S100A4-Dependent and-Independent Mechanisms. Cancers 2018, 10, 239.

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