Evidence map›Paper›PMID 42627588›Full record

ArticleMolecular biology reports2026

WNK4 restrains endometrial cancer progression by reprogramming macrophage polarization toward an M1-like phenotype.

Jiarong He, Tian Zhang, Menglan Xiong, Jing Zhao, Ziqing Wan, Guang Li, Qi Tian, Pu Zhang, Chuqiang Shu

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular biology reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Jiarong He *NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, No.53 Xiangchun Road, Changsha city, 410008, Hunan province, China.
Tian Zhang *NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, No.53 Xiangchun Road, Changsha city, 410008, Hunan province, China.
Menglan Xiong *NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, No.53 Xiangchun Road, Changsha city, 410008, Hunan province, China.
Jing ZhaoNHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, No.53 Xiangchun Road, Changsha city, 410008, Hunan province, China.
Ziqing WanNHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, No.53 Xiangchun Road, Changsha city, 410008, Hunan province, China.
Guang LiNHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, No.53 Xiangchun Road, Changsha city, 410008, Hunan province, China.
Qi TianNHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, No.53 Xiangchun Road, Changsha city, 410008, Hunan province, China. qi-tian@hotmail.com.
Pu ZhangNHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, No.53 Xiangchun Road, Changsha city, 410008, Hunan province, China. 13481717@qq.com.
Chuqiang ShuNHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, No.53 Xiangchun Road, Changsha city, 410008, Hunan province, China. chuqiang-shu@hotmail.com.

Funding

Innovation group foundation of Hunan Province Provincial maternal and Child health care hospital 2023RX03Innovation Platform and Talent Program of Hunan Province 2021SK4021Natural Science Foundation of Hunan Province 2026JJ30176
6 · The paper itself

Abstract

backgroundEndometrial cancer lacks robust immune-linked biomarkers that can be translated into tractable therapeutic strategies. WNK4, a member of the with-no-lysine (WNK) kinase family, is involved in cancer-relevant signaling pathways; however, its immunological significance in endometrial cancer has yet to be defined.

methodsImmune deconvolution and gene-immune correlation analyses were performed to relate WNK4 to immune-cell-associated signatures. WNK4 expression was assessed in clinical endometrial cancer tissues and cell lines by immunoblotting. Macrophage polarization was modeled using phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophages with interleukin-4 (IL-4) induction, followed by WNK4 overexpression. Polarization status was evaluated by marker expression and flow cytometry. Conditioned macrophage states were tested in Transwell co-culture with Ishikawa and HEC-1-A cells to assess viability, clonogenicity, migration/invasion, and apoptosis. To confirm the impact on tumor growth and macrophage-marker expression within tumors, we established a nude-mouse xenograft model.

resultsWNK4 was reduced in endometrial cancer tissues and malignant endometrial cell lines. Correlation analyses linked WNK4 to immune-state features, including an inverse association with M2-like macrophage signatures. In THP-1-derived macrophages, WNK4 overexpression counteracted IL-4-driven M2-like polarization and shifted cells toward an M1-like profile. In co-culture, WNK4-modified macrophages suppressed proliferative and motile phenotypes of endometrial cancer cells and increased apoptotic signaling. In vivo, WNK4 overexpression inhibited xenograft growth and was accompanied by macrophage-marker changes consistent with reduced M2-like features.

conclusionsWNK4 acts as an immune-relevant suppressor in endometrial cancer, partly by limiting M2-like polarization and weakening macrophage-driven tumor support.

Indexed as

Endometrial NeoplasmsMacrophagesProtein Serine-Threonine KinasesAnimalsCell DifferentiationCell Line, TumorCell MovementCell ProliferationCoculture TechniquesDisease ProgressionFemaleGene Expression Regulation, NeoplasticHumansInterleukin-4Macrophage ActivationMiceInterleukin-4Protein Serine-Threonine Kinasesendometrial cancermacrophage polarizationtumor-associated macrophagestumor microenvironmentWNK4

Identifiers

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.