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Stress-induced phosphoprotein 1: how does this co-chaperone influence the metastasis steps?

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Abstract

In several cancer types, metastasis is associated with poor prognosis, survival, and quality of life, representing a life risk more significant than the primary tumor itself. Metastasis is a multi-step process that spreads tumor cells from primary sites to surrounding or distant organs, originating secondary tumors. The interconnected steps that drive metastasis depend of several capabilities that enable cells to detach from the primary tumor, acquire motility and migrate through the basal membrane; invade and spread through the vascular system, and finally settle and originate a new tumor. Recently, stress-induced phosphoprotein 1 (STIP1) has emerged as a protein capable of driving tumor cells through these metastasis steps by mediating several biological processes and signaling pathways. This protein is mainly known for its function as a co-chaperone, acting as a scaffold for the interaction of its client heat-shock proteins Hsp70/90 chaperones; however, it is also known that STIP1 can act independently of chaperones to activate downstream phosphorylation pathways. The over-expression of STIP1 has been reported across various cancer types, identifying it as a potential biomarker for predicting patient prognosis and monitoring the progression of metastasis. Here, we present a discussion on how this co-chaperone mediates the initial steps of metastasis (cell adhesion loss, epithelial-to-mesenchymal transition, and angiogenesis), highlighting the biological mechanisms in which STIP1 plays a vital role, also presenting an overview of the current knowledge regarding its clinical relevance.

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Funding

This study was financed by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Process: 408730/2018-8

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  1. Genetics Post-Graduation Program, Genetics Department, Federal University of Paraná, P.O. box 19071, Curitiba, Paraná, CEP: 81531-990, Brazil

    Alexandre Luiz Korte de Azevedo, Talita Helen Bombardelli Gomig & Enilze Maria de Souza Fonseca Ribeiro

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All authors contributed to the review conception and design. Literature search and data analysis was performed by Alexandre Luiz Korte de Azevedo. The first draft of the manuscript was written by Alexandre Luiz Korte de Azevedo, and all authors commented on the subsequent versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Enilze Maria de Souza Fonseca Ribeiro.

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de Azevedo, A.L.K., Gomig, T. & Ribeiro, E.M.d.S.F. Stress-induced phosphoprotein 1: how does this co-chaperone influence the metastasis steps?. Clin Exp Metastasis (2024). https://doi.org/10.1007/s10585-024-10282-6

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