Expression and inactivation of osteopontin-degrading PHEX enzyme in squamous cell carcinoma

Expression and inactivation of osteopontin-degrading PHEX enzyme in squamous cell carcinoma

Author Neves, Raquel L. Autor UNIFESP Google Scholar
Chiarantin, Gabrielly M. D. Autor UNIFESP Google Scholar
Nascimento, Fabio D. Google Scholar
Pesquero, Joao B. Autor UNIFESP Google Scholar
Nader, Helena B. Autor UNIFESP Google Scholar
Tersariol, Ivarne L. S. Autor UNIFESP Google Scholar
McKee, Marc D. Google Scholar
Carmona, Adriana K. Autor UNIFESP Google Scholar
Barros, Nilana M. T. Autor UNIFESP Google Scholar
Abstract Proteolytic enzymes mediate the activation or inactivation of many physiologic and pathologic processes. The PHEX gene (Phosphate-regulating gene with homologies to endopeptidase on the X chromosome) encodes a metallopeptidase, which is mutated in patients with a prevalent form (1:20,000) of inherited rickets-X-linked hypophosphatemia (XLH). XLH shows growth retardation, hypophosphatemia, osteo-malacia, and defective renal phosphate reabsorption and metabolism of vitamin D. Most PHEX studies have focused on bone, and recently we identified osteopontin (OPN) as the first protein substrate for PHEX, demonstrating in the murine model of XLH (Hyp mice) an increase in OPN that contributes to the osteomalacia. Besides its role in bone mineralization, OPN is expressed in many tissues, and therein has different functions. In tumor biology, OPN is known to be associated with metastasis. Here, we extend our PHEX-OPN studies to investigate PHEX expression in a squamous cell carcinoma (SCC) cell line and its possible involvement in modulating OPN function. Real-time PCR showed PHEX-OPN co-expression in SCC cells, with sequencing of the 22 exons showing no mutation of the PHEX gene. Although recombinant PHEX hydrolyze SCC-OPN fragments, unlike in bone cells, SCC-PHEX protein was not predominantly at the plasma membrane. Enzymatic activity assays, FACs and immunoblotting analyses demonstrated that membrane PHEX is degraded by cysteine proteases and the decreased PHEX activity could contribute to inappropriate OPN regulation. These results highlight for the first time PHEX in tumor biology. (C) 2016 Elsevier Ltd. All rights reserved.
Keywords PHEX
Squamous cell carcinoma
xmlui.dri2xhtml.METS-1.0.item-coverage Oxford
Language English
Sponsor FAPESP (Fundacao de Amparo a Pesquisa do Estado de sao Paulo)
CNPq (Conselho Nacional de Desenvolvimento Cientlfico e Tecnologico)
Grant number FAPESP: 2011/504950
FAPESP: 2012/224801
CNPq: 478936/2013-3
Date 2016
Published in International Journal Of Biochemistry & Cell Biology. Oxford, v. 77, p. 155-164, 2016.
ISSN 1357-2725 (Sherpa/Romeo, impact factor)
Publisher Pergamon-Elsevier Science Ltd
Extent 155-164
Access rights Closed access
Type Article
Web of Science ID WOS:000381649800018

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