Banca de DEFESA: LUIZ ARTHUR BARBOSA DA SILVA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : LUIZ ARTHUR BARBOSA DA SILVA
DATE: 18/02/2020
TIME: 14:00
LOCAL: SALA VII DO DEPARTAMENTO DE ODONTOLOGIA
TITLE:

ANALYSIS OF BIOLOGICAL EFFECTS ASSOCIATED WITH HEAT SHOCK FACTOR 1 (HSF1) IN ORAL SQUAMOUS CELL CARCINOMA

KEY WORDS:

Squamous Cell Carcinoma; Prognosis, Tumor Biomarkers; Heat Shock Response

PAGES: 63
BIG AREA: Ciências da Saúde
AREA: Odontologia
SUMMARY:

Oral squamous cell carcinoma (OSCC) exhibits high rates of morbimortality and it is crucial to identify prognostic factors (clinicopathological and molecular) that have an impact on patient survival and that can stratify them in individualized therapies. In this perspective, there is the heat shock factor 1 (HSF1), considered the main activated transcription factor in response to proteotoxic stress, a common event in cancer cells. Evidences in various types of cancer show that different processes associated with tumor initiation and progression, as well as therapeutic resistance, are regulated by HSF1. Therefore, to clarify the pathways of HSF1 participation in the OSCC may help in the understanding of its biological behavior. In research previously developed by our group, a clinicopathological analysis and an immunoexpression study of HSF1 of 70 cases of oral tongue squamous cell carcinoma (OTSCC) were performed in comparison with 30 samples of the normal oral mucosa (NOM). In this current investigation, the role of HSF1 in OTSCC tumorigenesis was evaluated, through in vitro experiments with the SCC15 cell line, silenced and non-silenced with lentiviral particles, with silencing confirmed by qRT-PCR and Western Blot. Cell viability and proliferation (CellTiter and BrdU, respectively), invasion capacity (transwell / Matrigel system), influence on cell cycle (propidium iodide and flow cytometry analysis) and epithelial-mesenchymal (EMT) (expression of E-cadherin and vimentin by qRT-PCR) were evaluated. All in vitro experiments were repeated in triplicate and for all statistical tests used the significance level was 5%. Our previous results showed that as for the cases of OTSCC, 57.1% exhibited clinical stage III or IV, 82.9% were graded as high grade according to Bryne (1998), 47.1% as high risk according to Brandwein-Gensler et al. (2005) and 58.8% as high risk according to the BD model. It was observed an impact of Bryne's gradation (1998) (p = 0.05) on disease-free survival and of tumor size T3 or T4 (p = 0.04), local recurrence (p = 0.02) and BD model (p = 0.02) on global survival. A significant initial result (p <0.01) was found when comparing an HSF1 immunoexpression between NOM and OTSCC, with no significant association of immunoexpression with clinicopathological tests. From the functional studies, it was observed that HSF1 is overexpressed in the SCC15 cell line compared to normal keratinocytes (p <0.005) and that the silencing of this gene inhibited cell proliferation (p <0.005), advance in the cell cycle phases, with an increase in the number of cells in phases G0/G1 (p <0.01) and reduction of cells in phase S (p <0.001), invasion capacity (p <0.05) and EMT, with decreased vimentin expression (p <0.05) and increased E-cadherin (p <0.001), when compared to silenced and control lines. Given these results, it is suggested that HSF1 can exert a range of functions that maintain cell viability amid the stressful conditions of the tumor microenvironment. Thus, in the future, strategies involving its suppression may be a useful therapeutic tool in controlling the progress of the OSCC.

BANKING MEMBERS:
Externa à Instituição - BÁRBARA VANESSA DE BRITO MONTEIRO - UFCG
Externo à Instituição - CASSIANO FRANCISCO WEEGE NONAKA - UEPB
Interna - 1258693 - LELIA MARIA GUEDES QUEIROZ
Presidente - 1298808 - MARCIA CRISTINA DA COSTA MIGUEL
Externo ao Programa - 2318723 - SERGIO ADRIANE BEZERRA DE MOURA