Evidence map›Paper›PMID 41776586›Full record

ArticleMolecular cancer2026

Orosomucoid 2 promotes colorectal cancer liver metastasis by suppressing natural killer cell-mediated antitumor immunity by remodeling the serine and one-carbon metabolism pathway.

Jiamin Zhou, Xigan He, Zhen Xiang, Miao Wang, Weiqi Xu, Yixiu Wang, Yixin Chen, Ti Zhang, Lu Wang, Anrong Mao

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Jiamin Zhou *Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, P. R. China.
Xigan He *Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, P. R. China.
Zhen Xiang *Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, P. R. China.
Miao WangDepartment of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, P. R. China.
Weiqi XuDepartment of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, P. R. China.
Yixiu WangDepartment of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, P. R. China.
Yixin ChenDepartment of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, P. R. China.
Ti ZhangDepartment of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, P. R. China.
Lu WangDepartment of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, P. R. China. wangluzl@fudan.edu.cn.
Anrong MaoDepartment of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, P. R. China. 13020143060@163.com.

Funding

National Natural Science Foundation of China 82103556National Natural Science Foundation of China 82303395
6 · The paper itself

Abstract

backgroundThe liver is the most common site of distant metastasis in colorectal cancer (CRC), and liver metastasis (LM) remains the leading cause of CRC-related mortality. The immune microenvironment plays a crucial role in regulating LM progression, but the key molecular drivers involved in its remodeling remain poorly understood.

methodsWe performed an in vivo CRISPR-Cas9 screen in a murine model of colorectal cancer liver metastasis (CRLM) to identify key regulators of metastatic colonization. In vitro and in vivo functional studies were conducted to evaluate the role and mechanisms of ORM2 in modulating CRLM.

resultsWe identified orosomucoid 2 (ORM2) as a top candidate whose knockout markedly suppressed CRLM. Clinically, ORM2 expression was significantly upregulated in CRLM tissues and correlated with poor patient prognosis. Genetic ablation of ORM2 significantly reduced LM in vivo. Mechanistically, the pro-metastatic role of ORM2 was dependent on natural killer (NK) cells. Further analyses revealed that ORM2 interacts with activin A receptor type 1 (ACVR1) to activate the Hippo signaling pathway, leading to the suppression of serine and one-carbon metabolism, a key pathway for NK cell cytotoxic function.

conclusionsOur findings uncover a novel immunometabolic mechanism by which tumor-derived ORM2 promotes immune evasion and liver metastasis in CRC. Targeting the ORM2–ACVR1 axis may offer a promising therapeutic strategy for CRLM.

Indexed as

CarbonColorectal NeoplasmsKiller Cells, NaturalLiver NeoplasmsOrosomucoidSerineAnimalsCell Line, TumorDisease Models, AnimalGene Expression Regulation, NeoplasticHumansMiceSignal TransductionCarbonOrosomucoidSerineColorectal cancer liver metastasisNatural killer cellsORM2Serine and one-carbon metabolism

Identifiers

PMID41776586
PMCPMC13067650

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.