Scientists in China have uncovered a molecular pathway that helps colorectal cancer grow and spread by hijacking the immune system’s first responders. The study, published in Cellular and Molecular Life Sciences, shows that a protein called MCM10, long known simply as a component of the cellular DNA replication machinery, is far more than a passive workhorse inside dividing cells. In colorectal cancer, the researchers found, MCM10 is dramatically overproduced, and its excess levels fuel tumor growth while simultaneously coaxing nearby macrophages into a state that helps, rather than fights, the cancer. The work, led by Qiao Qu, Zhilong Li, Dalu Wang, Di Wu and senior author Hongzhuan Yin of Shengjing Hospital of China Medical University in Shenyang, also identifies the epigenetic mechanism that keeps MCM10 levels abnormally high, pointing to potential new targets for therapy in one of the world’s leading causes of cancer death.
The investigation began as a search for oncogenic drivers hidden in plain sight. The team performed RNA sequencing on seven pairs of colorectal tumor samples and matched adjacent normal tissue, comparing gene expression across each pair. Among the transcripts that stood out was MCM10, which was upregulated more than four-fold in tumor tissue, a log2 fold change of 2.359 with a statistical significance of P = 0.003. To make sure the signal was not an artifact of a small sample set, the researchers turned to two publicly available gene expression datasets, GSE240623 and GSE200427, both of which independently confirmed that MCM10 is overexpressed in colorectal cancer tissues. The final validation came from the clinic itself: in 40 paired samples of tumor and healthy tissue from patients, quantitative PCR and Western blotting both showed elevated MCM10 at the messenger RNA and protein levels.
The clinical stakes became clear when the team examined how MCM10 levels related to patient outcomes. Using hazard ratio analysis, they found that patients whose tumors expressed higher amounts of MCM10 fared significantly worse, with a hazard ratio of 1.54 and a P value of 0.00077. In practical terms, elevated MCM10 signaled roughly a 54 percent increase in the risk of adverse outcomes. MCM10 belongs to the minichromosome maintenance family of proteins, which assemble the molecular machinery that unwinds and copies DNA before cell division. That a replication factor should correlate with prognosis is not entirely surprising, since fast-dividing tumors need robust DNA synthesis. But the new study suggests MCM10 does something more sinister: it actively reshapes the tumor’s immune environment.
To test what MCM10 actually does inside cancer cells, the researchers ran a battery of functional experiments both in cell cultures and in living animals. When they forced colorectal cancer cells to overproduce MCM10, the cells proliferated faster and invaded more aggressively through laboratory matrices that mimic tissue barriers. Conversely, dialing MCM10 down blunted these malignant behaviors. In mouse models bearing tumor xenografts, overexpression of MCM10 produced larger, more invasive tumors. But the most striking observation came when the team looked at the immune cells infiltrating those tumors: the MCM10-overexpressing growths harbored far more macrophages of the so-called M2 type, with the proportion of M2-polarized macrophages rising from 6.16 percent plus or minus 0.85 percent in control tumors to 11.7 percent plus or minus 1.13 percent, a statistically significant difference.
M2 macrophages are often described as the tumor’s collaborators. Macrophages, the immune system’s resident scavengers, are not a single uniform population but a spectrum of states. The M1 end of the spectrum is inflammatory and generally hostile to tumors, while the M2 end is associated with wound healing, tissue repair and immune suppression. Tumors exploit this plasticity by releasing chemical signals that push infiltrating macrophages toward the M2 state, effectively converting the immune cells into cheerleaders for tumor growth, angiogenesis and metastasis. The Chinese team’s finding that MCM10 increases M2 infiltration raised an obvious question: how does a replication protein inside a cancer cell reprogram immune cells outside it?
The answer lies in the molecules that cancer cells secrete. The researchers collected conditioned media, the nutrient broth in which MCM10-overexpressing cancer cells had been growing, and applied it to THP-1 cells, a human cell line widely used as a model for macrophages. The treated macrophages shifted measurably toward the M2 phenotype. Biochemical analysis of the conditioned media revealed why: cancer cells burdened with excess MCM10 secreted elevated amounts of three signaling molecules, CCL2, CCL5 and IL10. CCL2 and CCL5 are chemokines, attractant proteins that recruit immune cells into the tumor, while IL10 is a potent anti-inflammatory cytokine that suppresses immune attack. Together, this molecular cocktail both draws macrophages to the tumor and instructs them to adopt the tumor-friendly M2 identity, creating a self-reinforcing cycle of immune suppression.
With MCM10’s role in tumor progression and immune evasion established, the team turned to the question of why the protein is overproduced in colorectal cancer in the first place. The culprit they identified is a chemical modification of messenger RNA known as N6-methyladenosine, or m6A, the most abundant internal modification in eukaryotic messenger RNA. The m6A mark is written onto RNA molecules by enzymes including METTL3, the primary methyltransferase of the writer complex, and its effects on a given transcript depend on which reader proteins recognize the mark. YTHDF1 is one such reader, and it generally promotes the translation of m6A-tagged transcripts into protein.
Working in HCT116, a well-established colorectal cancer cell line, the researchers demonstrated that METTL3 deposits m6A marks on the MCM10 messenger RNA, and that YTHDF1 then binds these marks and stabilizes the transcript. The consequence is a longer-lived MCM10 message and therefore more MCM10 protein. When either METTL3 or YTHDF1 is removed from the equation, the MCM10 mRNA degrades more quickly and protein levels fall, weakening the cancer-promoting behaviors that depend on it. This places MCM10 within a broader and rapidly expanding body of research showing that m6A modifications act as master regulators of cancer biology, controlling not just which genes are active but how long their instructions persist inside the cell.
The study carries the signature of modern cancer immunology, in which the tumor microenvironment is understood as an ecosystem rather than a mass of malignant cells. By linking an epigenetic RNA modification to a replication protein and then to immune polarization, the work traces a continuous causal chain from chemical mark to clinical outcome. It also offers a plausible explanation for why colorectal cancers with high MCM10 expression behave so aggressively: they are not merely growing faster, they are actively recruiting and reprogramming the immune cells that should be destroying them.
For clinicians and drug developers, the findings suggest several points of intervention. Blocking the METTL3-YTHDF1 axis could starve tumors of their MCM10 supply, and inhibitors targeting METTL3 are already under development in academic and industrial laboratories. Alternatively, disrupting the CCL2, CCL5 or IL10 signals could prevent the recruitment and polarization of M2 macrophages even when MCM10 remains high, potentially complementing existing immunotherapies. The authors, who received no external funding for the study, published their work as open access under a Creative Commons license, and note that the research was approved by the Ethics Committee of Shengjing Hospital affiliated to China Medical University. While the road from a cell culture dish and a mouse xenograft to an approved therapy is long, the identification of a druggable RNA modification pathway governing both tumor cell behavior and immune evasion gives researchers a promising new foothold against colorectal cancer.
Subject of Research: The role of MCM10, regulated by METTL3/YTHDF1-mediated m6A modification, in colorectal cancer progression through induction of M2 macrophage polarization
Subject of Research: Biology
Article Title: MCM10, regulated by METTL3/ YTHDF1-mediated m6A modification, contributes to colorectal cancer progression through induction of M2 macrophage polarization
Article References: Qu, Q., Li, Z., Wang, D., Wu, D., & Yin, H. (2026). MCM10, regulated by METTL3/ YTHDF1-mediated m6A modification, contributes to colorectal cancer progression through induction of M2 macrophage polarization. Cellular and Molecular Life Sciences. https://doi.org/10.1007/s00018-026-06425-5
Image Credits: AI Generated
DOI: 10.1007/s00018-026-06425-5
Keywords: Colorectal cancer, MCM10, METTL3, YTHDF1, N6-methyladenosine, m6A modification, Macrophage polarization, M2 macrophages, Tumor microenvironment, CCL2, IL10, mRNA stabilization
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Nathaniel Bowman. (September 7, 2026). MCM10 drives colorectal cancer progression via m6A-regulated M2 macrophage polarization. Scienmag. https://scienmag.com/mcm10-drives-colorectal-cancer-progression-via-m6a-regulated-m2-macrophage-polarization/
Nathaniel Bowman. “MCM10 drives colorectal cancer progression via m6A-regulated M2 macrophage polarization.” Scienmag, 7 September 2026, https://scienmag.com/mcm10-drives-colorectal-cancer-progression-via-m6a-regulated-m2-macrophage-polarization/. Accessed 7 September 2026.
Nathaniel Bowman. “MCM10 drives colorectal cancer progression via m6A-regulated M2 macrophage polarization.” Scienmag. September 7, 2026. https://scienmag.com/mcm10-drives-colorectal-cancer-progression-via-m6a-regulated-m2-macrophage-polarization/
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Tags: colorectal cancer progressionepigenetic regulation of MCM10epigenetic regulation of oncogenesimmune evasion mechanisms in colorectal cancerimmune system hijacking by tumorsM2 macrophage polarization in cancerM2 macrophage polarization in tumorsm6A RNA methylation in cancerm6A RNA modification in tumor growthMCM10 and immune system hijackingMCM10 protein in cancerMCM10 protein overexpressionmolecular pathways in colorectal cancermolecular pathways of tumor growthpotential therapeutic targets in cancerpotential therapeutic targets in colorectal cancerRNA sequencing in cancer researchrole of DNA replication proteins in cancerrole of DNA replication proteins in tumor developmenttumor microenvironment and immune responsetumor microenvironment modulationtumor-associated macrophages and cancer progression
