Evidence map›Paper›PMID 42018204›Full record

ArticleCellular oncology (Dordrecht, Netherlands)2026

The MIF-CD74 axis drives colorectal cancer via glycolytic reprogramming and is targeted by a novel small-molecule inhibitor.

Jinwei Lou, Yuhan Chen, Yue Li, Zixuan Liu, Shangshang Hu, Muzi Ding, Jian Qin, Huiling Sun, Yuqin Pan

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Article in Cellular oncology (Dordrecht, Netherlands), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Jinwei Lou *General Clinical Research Center, Nanjing First Hospital, China Pharmaceutical University, Nanjing, Jiangsu, 211122, China.
Yuhan Chen *General Clinical Research Center, Nanjing First Hospital, China Pharmaceutical University, Nanjing, Jiangsu, 211122, China.
Yue LiGeneral Clinical Research Center, Nanjing First Hospital, China Pharmaceutical University, Nanjing, Jiangsu, 211122, China.
Zixuan LiuGeneral Clinical Research Center, Nanjing First Hospital, China Pharmaceutical University, Nanjing, Jiangsu, 211122, China.
Shangshang HuGeneral Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China.
Muzi DingGeneral Clinical Research Center, Nanjing First Hospital, China Pharmaceutical University, Nanjing, Jiangsu, 211122, China.
Jian QinGeneral Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China.
Huiling SunGeneral Clinical Research Center, Nanjing First Hospital, China Pharmaceutical University, Nanjing, Jiangsu, 211122, China. sunhuiling1988@yeah.net.
Yuqin PanGeneral Clinical Research Center, Nanjing First Hospital, China Pharmaceutical University, Nanjing, Jiangsu, 211122, China. panyuqin@njmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMacrophage migration inhibitory factor (MIF) promotes inflammation, regulates immune responses and chemotherapy resistance in the tumor microenvironment. However, its mechanism of action in colorectal cancer (CRC) metabolic reprogramming and targeted therapeutic potential remain unclear. This study aims to investigate the function, mechanism, and targeted therapeutic potential of MIF in CRC.

methodsData were integrated from TCGA, GTEx, CPTAC, and HPA databases with clinical sample validation. Single-cell sequencing analysis (datasets GSE166555 and GSE144735) was performed, alongside functional assays and mechanistic studies. A novel high-potency MIF inhibitor was identified through virtual screening and validated in vitro and in vivo.

resultsMIF expression was found to be significantly elevated in CRC tissues and cell lines, correlating with poor overall survival (OS) and disease-specific survival (DSS). Single-cell sequencing confirmed malignant epithelial cells as the primary MIF source. Functional assays demonstrated that MIF knockout suppressed CRC cell proliferation, migration, and tumor growth in vivo, while MIF overexpression promoted these effects. Mechanistically, MIF binds CD74 to upregulate glycolytic enzymes (HK2, PKM2, LDHA), enhancing glucose uptake and lactate/pyruvate production, thereby driving the Warburg effect and CRC progression. Virtual screening identified a novel high-potency MIF inhibitor, F3277-0933 (IC50 = 8.284 μM). In vitro and in vivo, F3277-0933 surpassed the classical inhibitor ISO-1 in suppressing MIF-driven glycolytic reprogramming and proliferation.

conclusionThis study elucidates a novel mechanism by which the MIF-CD74 axis drives CRC progression through glycolytic reprogramming and provides robust preclinical evidence for developing MIF-targeted therapies.

Indexed as

Antigens, Differentiation, B-LymphocyteColorectal NeoplasmsGlycolysisHistocompatibility Antigens Class IIIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsSmall Molecule LibrariesAnimalsCell Line, TumorCell MovementCell ProliferationGene Expression Regulation, NeoplasticHumansMetabolic ReprogrammingMiceMice, NudeAntigens, Differentiation, B-LymphocyteHistocompatibility Antigens Class IIIntramolecular Oxidoreductasesinvariant chainMacrophage Migration-Inhibitory FactorsMIF protein, humanSmall Molecule LibrariesCD74 receptorColorectal cancerF3277-0933Glycolytic reprogrammingMacrophage migration inhibitory factor (MIF)Small-molecule inhibitor

Identifiers

PMID42018204
PMCPMC13103017

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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.