Epigenetic control of WNT/b-catenin signaling in chemoresistant cancer stem cells accumulation in oral carcinoma

• Grant number: 20/02740-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2020
• End date: July 31, 2022
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Luciana Oliveira de Almeida
• Grantee: Thaís Moré Milan
• 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

Oral carcinoma is responsible for many deaths around the world and it has high capacity to develop recurrences and metastases due to failures in therapy promoted by chemoresistance. Conventional treatments such as radio and chemotherapy are capable of destroying differentiated cells of the tumor, but a small population called cancer stem cells remains intact and repopulates the tumor. Many pathways are found deregulated in cancer stem cells, and the Wnt/²-catenin signaling pathway is related to the maintenance, survival, self-renewal and differentiation of cancer stem cells, besides being related to the initiation of several tumors. In head and neck carcinoma, overctivation of the Wnt/²-catenin pathway is associated with epigenetic modifications that keep the chromatin structure opened, inducing gene activation that lead to accumulation of cancer stem cells. Moreover, enzymes involved in epigenetic regulation can also inhibit Wnt/²-catenin signaling through chromatin condensation leading to gene repression. Therefore, seeking to elucidate the mechanisms that contribute to the regulation of target genes of WNT signaling may have important implications for the development of new therapeutic strategies for the effective elimination of cancer stem cells. This project aims to identify epigenetic modifications involved in the Wnt/²-catenin signaling and its targets and investigate the involvement of this pathway in the accumulation of cancer stem cells and in the chemoresistance of oral carcinoma cell lines. (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)

MILAN, THAIS MORE; ESKENAZI, ANA PATRICIA ESPALADORI; DE OLIVEIRA, LUCAS DIAS; DA SILVA, GABRIEL; BIGHETTI-TREVISAN, RAYANA LONGO; FREITAS, GILEADE PEREIRA; ALMEIDA, LUCIANA OLIVEIRA. Interplay between EZH2/β-catenin in stemness of cisplatin-resistant HNSCC and their role as therapeutic targets. CELLULAR SIGNALLING, v. 109, p. 13-pg., 2023-09-01. (20/02740-5, 17/11780-8)

Academic Publications

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

MILAN, Thaís Moré. Epigenetic control of Wnt/β-catenin signaling pathway in the accumulation of chemoresistant cancer stem cells in oral carcinoma. 2022. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.