MACC1 in colorectal cancer: a claim-level evidence audit from metastasis driver to proposed microenvironmental regulator.

Metastasis-associated in colon cancer 1 (MACC1) is an established regulator of colorectal cancer (CRC) progression and metastatic competence, but its proposed role in the tumour microenvironment is less certain. We performed a critical claim-level audit of original studies, classifying evidence by cancer-type match, manipulated cellular compartment, direct MACC1 perturbation, functional recipient cell endpoint, and immune context. The audit identifies convergent CRC evidence for tumour cell-intrinsic functions and inflammatory regulation of tumour cell MACC1. It also supports MACC1-dependent extracellular vesicle communication between CRC cells. By contrast, direct immune or stromal causality in CRC is not yet demonstrated: the available macrophage result is pharmacologically conditioned, functional immune and fibroblast mechanisms come from other cancers, and CRC immune associations are mainly computational. We define the conclusions permitted by each evidence class, specify clinical guardrails for prognostic and treatment-predictive claims, and propose two experiments that could establish or falsify cell-specific microenvironmental functions.