The role of dendritic cell-derived amphiregulin in colorectal cancer progression.

• Grant number: 25/05036-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2025
• End date: June 30, 2028
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: José Carlos Farias Alves Filho
• Grantee: Matheus Brandemarte Severino
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

Colorectal cancer results from the accumulation of mutations in the DNA of colon cells, influenced by genetic and environmental factors. In Brazil, it is the second most common neoplasm, with high mortality rates despite the available therapies, such as surgery, chemotherapy, radiotherapy, and immunotherapy.Amphiregulin (AREG), a member of the EGF family, activates the EGFR receptor and triggers intracellular pathways such as MAPK, PI3K/AKT, and JAK/STAT, regulating cell proliferation and survival. Although AREG plays a role in tissue homeostasis and inflammation resolution, it is also involved in pathological processes, including cancer.Preliminary data indicate high AREG expression in colorectal cancer biopsies. In vitro assays with MC-38 cells show that AREG promotes proliferation and clonal expansion, suggesting its role in tumor progression. Additionally, single-cell analyses suggest that dendritic cells may be a relevant source of AREG in the tumor microenvironment.This may reflect an onco-immune interaction in colorectal cancer, where dendritic cells respond to tumor cells and contribute to cancer progression via AREG release. These findings could enable new therapeutic approaches to improve colorectal cancer treatment. (AU)