Impact of the stress-induced phosphoprotein 1 (STIP1) expression in oral squamous cell carcinoma

Abstract

In a comparative proteomic study between invasive and non-invasive cells of oral squamous cell carcinoma (OSCC), our group identified numerous proteins associated with invasive cells, including the stress-induced phosphoprotein 1 (STIP1). Although dysregulated STIP1 expression has been associated with malignancy phenotypes, therapeutic resistance, and poor prognosis in some types of tumors, the role of STIP1 in oral cancer has not yet been explored. For this reason, STIP1 was one of the proteins selected for an evaluation of its prognostic and biological value in OSCC (current research grant, number 2018/16077-6). Initially, we evaluated the prognostic value of STIP1 immunohistochemical expression in 347 OSCC samples and the results revealed a great potential of STIP1 as a prognostic marker and possible therapeutic target. In order to expand our knowledge, the aim of this project is to evaluate the impact of this protein on the viability, apoptosis, proliferation, migration, and invasion of OSCC cells. Therefore, two OSCC cell lines (HSC3 and SCC9), selected for presenting high levels of STIP1 expression, were subjected to a loss-of-function strategy based on the transduction of lentiviral particles containing shRNA against the mRNA of the target protein. Cells transduced with nonspecific lentiviral particles were established and will be used as a control. Functional assays, including MTS colorimetric assay, annexin-V FITC labeling, bromodeoxyuridine incorporation assay, cell cycle distribution analysis, colony formation assay, and migration and invasion assays, will be used to investigate the effect of this protein on oral tumorigenesis. Considering that none of the OSCC biomarkers suggested in the literature meet the criteria for clinical application, it is expected that this study can contribute to consolidating the importance of STIP1 in the control of events associated with the progression of OSCC, consolidating its potential as a marker to assess prognosis and/or therapeutic target for oral cancer.(AU)