Reprogramming of FACT complex as a potential therapeutic target in cancer-associated fibroblasts and oral carcinoma using zebrafish model.

• Grant number: 24/08728-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: April 01, 2025
• End date: November 30, 2025
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Andréia Machado Leopoldino
• Grantee: Graziella Ribeiro de Sousa
• Supervisor: Lasse Dahl Ejby Jensen
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Linköping University (LiU), Sweden
• Associated to the scholarship: 22/07171-4 - Investigation of control of histone chaperones by sphingosine kinase 2/S1P and its impact on the biogenesis of oral squamous cell carcinoma, BP.PD

Abstract

Late stage of oral squamous cell carcinoma (OSCC) is characterized by metastasis and high mortality rates. Cancer-associated fibroblasts (CAFs), especially the alpha smooth muscle actin positive subtype exert crucial influences on OSCC progression and metastasis through complex signaling pathways. However, the molecular mechanisms underlying CAF-induced OSCC progression and metastasis remain incompletely understood. Recent studies have highlighted the overexpression of histone chaperone Facilitates Chromatin Transcription (FACT) complex in various cancers and our preliminary data demonstrate its potential significance in OSCC pathogenesis. To elucidate the interplay between the FACT complex-CAFs and its role in metastasis, we will establish zebrafish xenografts based on OSCC cell lines and CAFs from patients. Our hypothesis posits that the FACT complex acts as a key mediator facilitating crosstalk between CAFs and OSCC cells, thereby promoting tumor growth, metastasis, and immune evasion. Importantly, our investigation proposes unrecognized role of the histone chaperone, FACT, associated with CAFs, which could shed light on previously unexplored avenues of therapeutic intervention in late-stage OSCC.