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

Mauricio Rocha Dourado, Amr Elseragy, Bruno Cesar da Costa, Fábio Haach Téo, Gustavo Narvaes Guimarães, Renato Assis Machado, Maija Risteli, Wafa Wahbi, Clarissa Araujo Gurgel Rocha, Lívia Máris Ribeiro Paranaíba, Wilfredo Alejandro González-Arriagada, Sabrina Daniela da Silva, Ana Lucia Carrinho Ayroza Rangel, Marcelo Rocha Marques, Carlos Rossa Junior, Tuula Salo, Ricardo D. Coletta*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number1085917
JournalFrontiers in Oncology
StatePublished - 11 Jan 2023

Bibliographical note

Funding Information:
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.

Publisher Copyright:
Copyright © 2023 Dourado, Elseragy, da Costa, Téo, Guimarães, Machado, Risteli, Wahbi, Gurgel Rocha, Paranaíba, González-Arriagada, da Silva, Rangel, Marques, Rossa Junior, Salo and Coletta.


  • invasion
  • MIR-218-5p
  • oral cancer
  • prognosis
  • proliferation
  • STIP1


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