Evidence map›Paper›PMID 41437376›Full record

ArticleMolecular cancer2025

Targeting the CD47-HCK-LGALS9 axis disrupts proliferation-immunosuppression coupling in early-stage endometrial cancer.

Jingxuan Ye, Yitong Yan, Xiaoqi Sun, Qibin Wu, Yashi Shi, Maotong Zhang, Xite Lin, Yuan Ren, Xiaodan Mao, Mingyan Lin and 1 more

Abstract read
In one paragraph

Article in Molecular cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. 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

11 authors.

Jingxuan Ye *Laboratory of Gynecologic Oncology, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Maternity and Child Health Hospital, Fujian Medical University, Fuzhou, Fujian, 350001, China.
Yitong Yan *Department of Neurobiology, School of Basic Medical Science, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
Xiaoqi Sun *Fujian Clinical Research Center for Gynecological Oncology, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital), Fuzhou, Fujian, 350001, China.
Qibin WuFujian Clinical Research Center for Gynecological Oncology, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital), Fuzhou, Fujian, 350001, China.
Yashi ShiLaboratory of Gynecologic Oncology, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Maternity and Child Health Hospital, Fujian Medical University, Fuzhou, Fujian, 350001, China.
Maotong ZhangLaboratory of Gynecologic Oncology, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Maternity and Child Health Hospital, Fujian Medical University, Fuzhou, Fujian, 350001, China.
Xite LinLaboratory of Gynecologic Oncology, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Maternity and Child Health Hospital, Fujian Medical University, Fuzhou, Fujian, 350001, China.
Yuan RenLaboratory of Gynecologic Oncology, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Maternity and Child Health Hospital, Fujian Medical University, Fuzhou, Fujian, 350001, China.
Xiaodan MaoLaboratory of Gynecologic Oncology, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Maternity and Child Health Hospital, Fujian Medical University, Fuzhou, Fujian, 350001, China. maodan1985@yeah.net.ORCID http://orcid.org/0000-0001-8242-914X
Mingyan LinDepartment of Neurobiology, School of Basic Medical Science, Nanjing Medical University, Nanjing, Jiangsu, 211166, China. linmingyan@njmu.edu.cn.ORCID http://orcid.org/0000-0003-3517-0432
Pengming SunLaboratory of Gynecologic Oncology, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Maternity and Child Health Hospital, Fujian Medical University, Fuzhou, Fujian, 350001, China. fmsun1975@fjmu.edu.cn.ORCID http://orcid.org/0000-0002-5072-6091

Funding

the National Key Research and Development Program of China 2022YFC2704303the National Nature Science Foundation of China 82203739
6 · The paper itself

Abstract

backgroundsSignificant heterogeneity was observed in the epithelial-derived endometrial cancer (EC), which contributes to different prognostic outcomes. While the mechanisms involved in this heterogeneity in the tumor microenvironment (TME) of early-stage EC remain poorly defined.

methodsSingle-cell RNA sequencing, spatial transcriptomics, and multiplex immunofluorescence (mIF) were applied to characterize cellular subpopulations in early-stage EC. EC cell proliferation was assessed by CCK-8 and flow cytometry (FC). Furthermore, the epithelial dynamics and macrophage interactions were also investigated in vitro by molecular docking and GST pull-down mass spectrometry. Phagocytic activity was also evaluated by FC and immunofluorescence. Moreover, the upstream transcription factors were identified using CUT&Tag. For in vivo study, an organoid–macrophage co-culture model was established to mimic the EC microenvironment, and altered organoid proliferation and macrophage phagocytosis were confirmed. CD47 was evaluated as a potential prognostic marker by proteomic analysis and immunohistochemistry.

resultsWe identified a previously unrecognized epithelial subpopulation (CD47⁺CDK1⁺) that was strongly linked to cell-cycle signaling and malignant proliferation. This subpopulation interacts closely with macrophages through the CD47–Galectin 9 (LGALS9) receptor-ligand pair. Functionally, CD47 inhibition suppressed EC cell proliferation and induced apoptosis, while CD47 overexpression enhanced the proliferative capacity of EC patient-derived organoids (PDOs). EC cells and PDOs engaged macrophages through the CD47–HCK (Hemopoietic Cell Kinase) axis, driving the secretion of immunosuppressive molecules LGALS9, IL-10, and TGF-β1 and forming an immunosuppressive TME. In turn, macrophage-derived LGALS9 reinforced EC cell and PDO proliferation via CD47, establishing a positive feedback loop involving CD47–HCK–LGALS9. Furthermore, estrogen-related receptor gamma (ERRγ) was identified as an upstream transcriptional regulator of CD47, and its expression was suppressed by progesterone.

conclusionsRegulated by ERRγ, an optimistic therapeutic target, the CD47-HCK-LGALS9 axis modulated cellular proliferation-immunosuppression coupling in early-stage EC.

Indexed as

CD47 AntigenEndometrial NeoplasmsGalectinsProto-Oncogene Proteins c-hckAnimalsCell Line, TumorCell ProliferationFemaleHumansMacrophagesMiceNeoplasm StagingSignal TransductionTumor MicroenvironmentCD47 AntigenCD47 protein, humanGalectinsProto-Oncogene Proteins c-hckCD47Cell cycleEndometrial cancerERRγHCKImmunosuppressive microenvironmentLGALS9

Identifiers

PMID41437376
PMCPMC12969882

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Registered trials

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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.