The glycolysis-H4K12la-PKM2 positive feedback loop drives M2 polarization of macrophages in colorectal cancer.

ABSTRACT:

Background

Despite the dominance of M2-polarized tumor-associated macrophages in colorectal cancer (CRC), the metabolic-epigenetic mechanisms by which CRC cells sustain this immunosuppressive phenotype remain elusive. We hypothesize that a glycolysis-driven positive feedback loop, involving PKM2-mediated lactate production and subsequent H4K12 lactylation (H4K12la) at the PKM2 promoter, enables CRC cells to metabolically reprogram macrophages toward M2 polarization. This study aims to characterize this regulatory circuit and determine its potential as a therapeutic target to enhance immunotherapy efficacy.

Methods

We used qRT-PCR, Western blot, and metabolic flux analysis (ECAR, lactate production, 2-NBDG uptake) to assess the glycolysis-H4K12la-PKM2 axis in CRC cells follow

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC13644130 | biostudies-literature | 2026 Jul

REPOSITORIES: biostudies-literature