University of Oulu

Dourado MR, Elseragy A, da Costa BC, Téo FH, Guimarães GN, Machado RA, Risteli M, Wahbi W, Gurgel Rocha CA, Paranaíba LMR, González-Arriagada WA, da Silva SD, Rangel ALCA, Marques MR, Rossa Junior C, Salo T and Coletta RD (2023) Stress induced phosphoprotein 1 overexpression controls proliferation, migration and invasion and is associated with poor survival in oral squamous cell carcinoma. Front. Oncol. 12:1085917. doi: 10.3389/fonc.2022.1085917

Stress induced phosphoprotein 1 overexpression controls proliferation, migration and invasion and is associated with poor survival in oral squamous cell carcinoma

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Author: Dourado, Mauricio Rocha1; Elseragy, Amr2; da Costa, Bruno Cesar1;
Organizations: 1Department of Oral Diagnosis, and Graduate Program in Oral Biology, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil
2Cancer and Translational Medicine Research Unit, Faculty of Medicine, and Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
3Department of Biosciences and Graduate Program in Oral Biology, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil
4Hospital for Rehabilitation of Craniofacial Anomalies, University of São Paulo (HRAC/USP), Bauru, São Paulo, Brazil
5Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, and Translational Immunology Research Program (TRIMM), University of Helsinki, Helsinki, Finland
6Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil
7Federal University of Bahia, Salvador, Bahia, Brazil
8Center for Biotechnology and Cell Therapy, D’Or Institute for Research and Education (IDOR), Salvador, Brazil
9Department of Pathology and Parasitology, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil
10Facultad de Odontología, and Centro de Investigación e Innovación Biomédica (CIIB), Universidad de los Andes, Santiago, Chile
11Lady Davis Institute for Medical Research and Segal Cancer Center, Jewish General Hospital, and Department of Otolaryngology-Head and Neck Surgery, McGill University, Montreal, QC, Canada
12Department of Oral Pathology and Oral Medicine, Dental School, Western Paranaí State University, Cascavel, Paraná, Brazil
13Department of Diagnosis and Surgery, School of Dentistry at Araraquara, São Paulo State University (UNESP), Araraquara, São Paulo, Brazil
14HUSLAB, Department of Pathology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 4.7 MB)
Persistent link:
Language: English
Published: Frontiers Media, 2023
Publish Date: 2023-07-13


Objective: Although there have been remarkable achievements in the molecular landscape of oral squamous cell carcinoma (OSCC) in recent years, bringing advances in the understanding of its pathogenesis, development and progression, little has been applied in the prognosis and choosing the optimal treatment. In this study, we explored the influence of the stress induced phosphoprotein 1 (STIP1), which is frequently reported to be highly expressed in many cancers, in OSCCs.

Methods: STIP1 expression was assessed in the TCGA database and in two independent cohorts by immunohistochemistry. Knockdown strategy was applied in OSCC cell lines to determine the impact of STIP1 on viability, proliferation, migration and invasion. The zebrafish model was applied for studying tumor formation and metastasis in vivo. The association of STIP1 and miR-218-5p was explored by bioinformatics and mimics transfection.

Results: STIP1 was highly expressed in OSCCs and significantly associated with shortened survival and higher risk of recurrence. STIP1 down-regulation decreased proliferation, migration and invasion of tumor cells, and reduced the number of metastases in the Zebrafish model. STIP1 and miR-218-5p were inversely expressed, and the transfection of miR-218-5p mimics into OSCC cells decreased STIP1 levels as well as proliferation, migration and invasion.

Conclusion: Our findings show that STIP1 overexpression, which is inversely associated with miR-218-5p levels, contributes to OSCC aggressiveness by controlling proliferation, migration and invasion and is a determinant of poor prognosis.

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Series: Frontiers in oncology
ISSN: 2234-943X
ISSN-E: 2234-943X
ISSN-L: 2234-943X
Volume: 12
Article number: 1085917
DOI: 10.3389/fonc.2022.1085917
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 2018/16077-6 to RC), and from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, 407814/2018-3 and 407814/2018-3 to RC). MD (2021/13595-9) and BC (2021/08943-8) were research fellows supported by FAPESP. AE, MR, WW and TS were funded by Universities of Oulu and Helsinki, the Sigrid Juselius Foundation, and Oulu and Helsinki University Hospital special state support for research.
Copyright information: © 2023 Dourado, Elseragy, da Costa, Téo, Guimarães, Machado, Risteli, Wahbi, Gurgel Rocha, Paranaíba, González-Arriagada, da Silva, Rangel, Marques, Rossa Junior, Salo and Coletta. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.