University of Oulu

Andreia Ferreira do Carmo, Mauricio Rocha Dourado, Carine Ervolino de Oliveira, Débora Campanella Bastos, Catherine Bueno Domingueti, Lívia Máris Ribeiro Paranaíba, Íris Sawazaki-Calone, Gabriel Álvares Borges, Eliete Neves Silva Guerra, Renato C. Casarin, Edgard Graner, Tuula A. Salo, Roseana de Almeida Freitas, Hébel Cavalcanti Galvão, Ricardo D. Coletta, Stanniocalcin 2 contributes to aggressiveness and is a prognostic marker for oral squamous cell carcinoma, Experimental Cell Research, Volume 393, Issue 2, 2020, 112092, ISSN 0014-4827, https://doi.org/10.1016/j.yexcr.2020.112092

Stanniocalcin 2 contributes to aggressiveness and is a prognostic marker for oral squamous cell carcinoma

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Author: Ferreira do Carmo, Andreia1,2; Rocha Dourado, Mauricio1; Ervolino de Oliveira, Carine3;
Organizations: 1Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, SP, Brazil
2Department of Dentistry, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil
3Department of Pathology and Parasitology, Institute of Biomedical Sciences, Federal University of Alfenas (UNIFAL-MG), Alfenas, Minas Gerais, Brazil
4Oral Pathology and Oral Medicine, Dentistry School, Western Paraná; State University, Cascavel, Paraná, Brazil
5Laboratory of Oral Histopathology, Health Sciences Faculty, University of Brasilia, Brasilia, Brazil
6Department of Prosthodontics and Periodontics, School of Dentistry, University of Campinas, Piracicaba, SP, Brazil
7Cancer and Translational Medicine Research Unit, Faculty of Medicine and Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland; Institute of Oral and Maxillofacial Disease, University of Helsinki, and HUSLAB, Department of Pathology, Helsinki University Hospital, Helsinki, Finland
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe2020061242925
Language: English
Published: Elsevier, 2020
Publish Date: 2021-05-20
Description:

Abstract

Stanniocalcin 2 (STC2), a glycoprotein that regulates calcium and phosphate homeostasis during mineral metabolism, appears to display multiple roles in tumorigenesis and cancer progression. This study aimed to access the prognostic value of STC2 in oral squamous cell carcinoma (OSCC) and its implications in oral tumorigenesis. STC2 expression was examined in 2 independent cohorts of OSCC tissues by immunohistochemistry. A loss-of-function strategy using shRNA targeting STC2 was employed to investigate STC2 in vitro effects on proliferation, apoptosis, migration, invasion, epithelial-mesenchymal transition (EMT) and possible activation of signaling pathways. Moreover, STC2 effects were assessed in vivo in a xenograft mouse cancer model. High expression of STC2 was significantly associated with poor disease-specific survival (HR: 2.67, 95% CI: 1.37–5.21, p = 0.001) and high rate of recurrence with a hazard ratio of 2.80 (95% CI: 1.07–5.71, p = 0.03). In vitro downregulation of STC2 expression in OSCC cells attenuated proliferation, migration and invasiveness while increased apoptotic rates. In addition, the STC2 downregulation controlled EMT phenotype of OSCC cells, with regulation on E-cadherin, vimentin, Snail1, Twist and Zeb2. The reactivation of STC2 was observed in the STC2 knockdown cells in the in vivo xenograft model, and no influence on tumor growth was observed. Modulation of STC2 expression levels did not alter consistently the phosphorylation status of CREB, ERK, JNK, p38, p70 S6K, STAT3, STAT5A/B and AKT. Our findings suggest that STC2 overexpression is an independent marker of OSCC outcome and may contribute to tumor progression via regulation of proliferation, survival and invasiveness of OSCC cells.

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Series: Experimental cell research
ISSN: 0014-4827
ISSN-E: 1090-2422
ISSN-L: 0014-4827
Volume: 393
Issue: 2
Article number: 112092
DOI: 10.1016/j.yexcr.2020.112092
OADOI: https://oadoi.org/10.1016/j.yexcr.2020.112092
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Subjects:
Funding: This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP (2018/16,077-6 for RDC). MRD (2017/26,764-8) is research fellow supported by FAPESP, and LMPR received a grant from the Fundação de Amparo à Pesquisa do Estado de Minas Gerais - FAPEMIG (APQ 00205.16).
Copyright information: © 2020 Elsevier Inc. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/.
  https://creativecommons.org/licenses/by-nc-nd/4.0/