Itaconate and obesity-related hormones promote tumor progression - new insights on metabolic dysfunction in early-onset colon cancer.

ABSTRACT:

Introduction

Obesity is a strong risk factor for early-onset colon cancer (EOCC) and is associated with chronic inflammation largely mediated by macrophages. The macrophage-specific metabolite itaconate promotes growth in several types of cancer; however, its role in colon cancer (CC) is unknown. Here, we investigate a tumor promoting link between obesity-related hormones and itaconate within the NOTCH4-GATA4-IRG1 pathway in EOCC.

Methods

Patient tissue (n=20) was obtained and qRT-PCR, ELISA, and mass spectrometry were performed to evaluate IRG1 expression (Human Immune-Responsive Gene 1, encoding ACOD1), ACOD1 expression (Cis-aconitate decarboxylase 1, enzyme producing itaconate), and itaconate concentration in human CC versus EOCC. RNA sequencing data from 5 sources

SUBMITTER: Scheurlen KM 

PROVIDER: S-EPMC12183228 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature