The role of HDAC6 in the regulation of oxidative stress and chemoresistance of cancer stem cells in oral carcinoma

• Grant number: 19/19301-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: December 01, 2019
• End date: November 30, 2021
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Luciana Oliveira de Almeida
• Grantee: Marcela de Oliveira Tavares
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 17/11780-8 - Study of epigenetic modifications related to cancer stem cells accumulation in head and neck cancer: implications in chemoresistance, AP.JP

Abstract

Chemoresistance is a major cause of failure in cancer therapy, increasing the risk of metastasis. Chemoresistance is initiated by a small group of cells identified as cancer stem cells. In oral carcinoma, the cancer stem cell population is accumulated after chemotherapy, and epigenetic modifications may be controlling this process. HDAC6 is a histone deacetylase found accumulated in cancer stem cells. HDACs are a group of deacetylase enzymes that epigenetically regulate chromatin organization and gene expression by removing acetyl groups from lysine residues in histones and nonhistone proteins. HDAC6 acts in several physiological processes, including oxidative stress response, autophagy and DNA damage response, and its accumulation is associated to the development of pathological disorders, such as cancer. Establishing efficient therapeutic strategies in cancer treatment is important to understand the epigenetic factors that promote chemoresistance, as well as exploring the behavior of tumor stem cells and the signaling that regulates their metabolism. This project aims to investigate the role of HDAC6 in the tumor resistance process mediated by cancer stem cells in oral carcinoma, evaluating the influence of HDAC6 on the DNA damage response and oxidative stress and its possible application as a potential therapeutic target to eliminate cancer stem cells and reverse chemoresistance. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TAVARES, MARCELA OLIVEIRA; MILAN, THAIS MORE; BIGHETTI-TREVISAN, RAYANA LONGO; LEOPOLDINO, ANDREIA MACHADO; DE ALMEIDA, LUCIANA OLIVEIRA. Pharmacological inhibition of HDAC6 overcomes cisplatin chemoresistance by targeting cancer stem cells in oral squamous cell carcinoma. JOURNAL OF ORAL PATHOLOGY & MEDICINE, v. N/A, p. 9-pg., 2022-06-28. (19/19301-7, 17/11780-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

TAVARES, Marcela de Oliveira. The role of HDAC6 in the regulation of oxidative stress and chemoresistance of tumor stem cells in oral carcinoma. 2022. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Odontologia de Ribeirão Preto (PCARP/BC) Ribeirão Preto.