Evidence map›Paper›PMID 42337536›Full record

ArticleJournal of translational medicine2026

A novel EGR1-driven GLUL/mTOR axis regulates macropinocytosis-mediated crosstalk in pancreatic stellate cell-cancer metastasis.

Ran Xue, Jun Zhou, Yawei Liu, Yuxi Liu, Jing Wu, Xinran Song

Abstract read
In one paragraph

Article in Journal of translational medicine, 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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0citing papers in PubMed
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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

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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

6 authors.

Ran Xue *Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Early Drug Development Center, Peking University Cancer Hospital & Institute, Fucheng Road 52, Haidian District, Beijing, 100142, China. xueran2@sina.com.
Jun Zhou *Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Fucheng Road 52, Haidian District, Beijing, 100142, China.
Yawei Liu *School of Basic Medicine, Capital Medical University, Beijing, 100069, China.
Yuxi Liu *School of Basic Medicine, Capital Medical University, Beijing, 100069, China.
Jing WuDepartment of Medical Oncology, Beijing You-An Hospital, Capital Medical University, Beijing, 100069, China.
Xinran SongSchool of Basic Medicine, Capital Medical University, Beijing, 100069, China.

Funding

Fund for Fostering Young Scholars of Peking University Health Science Center BMU2021PY010Medjaden Academy and Research Foundation for Young Scientists MJR20211110NATIONAL NATURAL SCIENCE FOUNDATION OF CHINA 82002461the Beijing Hospitals Authority Youth Programme QML20231104the Young Scientist Training Program - Key Project of Peking University Cancer Hospital Scientific Research Foundation BJCH2026GG03
6 · The paper itself

Abstract

backgroundPancreatic cancer liver metastasis relies on crosstalk between pancreatic stellate cells (PSCs) and cancer cells, yet the role of transcriptional regulation in this interplay, particularly via macropinocytosis, remains unclear. Here, we aimed to explore a novel EGR1-driven pathway linking PSC function to cancer cell nutrient acquisition and liver metastasis.

methodsSingle-cell RNA sequencing (scRNA-seq) was performed on human pancreatic cancer tissues to identify key regulators of PSC-cancer cell crosstalk. ChIP, EMSA, luciferase reporter assays, and western blotting were used to validate transcriptional regulation of GLUL by EGR1. Functional assays included cell proliferation, migration, invasion, and macropinocytosis analyses in co-culture systems. In vivo studies utilized a murine model of pancreatic cancer liver metastasis to assess the impact of the EGR1-GLUL/mTOR axis on metastasis.

resultsscRNA-seq identified EGR1 as a transcription factor enriched in PSCs, with strong co-expression of GLUL and mTOR pathway genes. EGR1 directly bound the GLUL promoter, promoting its transcription and activating mTOR signaling. This axis suppressed PSC activation (reduced α-SMA expression). EGR1 over-expressed PSCs inhibited pancreatic cancer cell macropinocytosis, leading to impaired nutrient uptake, reduced ATP production, and suppressed malignant behaviors (proliferation, migration, invasion). Additionally, the EGR1-GLUL/mTOR axis reduced liver metastasis in vivo.

conclusionThe EGR1-driven GLUL/mTOR axis in PSCs suppresses pancreatic cancer progression by inhibiting PSC activation, reducing cancer cell macropinocytosis, and restraining metastasis. This axis represents a promising therapeutic target for disrupting PSC-cancer cell crosstalk in pancreatic cancer.

Indexed as

Early Growth Response Protein 1Pancreatic NeoplasmsPancreatic Stellate CellsPinocytosisTOR Serine-Threonine KinasesAnimalsCell Line, TumorCell MovementCell ProliferationGene Expression Regulation, NeoplasticHumansLiver NeoplasmsMiceNeoplasm InvasivenessNeoplasm MetastasisPromoter Regions, GeneticEarly Growth Response Protein 1EGR1 protein, humanMTOR protein, humanTOR Serine-Threonine KinasesMacropinocytosisMetabolic reprogrammingMetastasisPancreatic cancerPancreatic stellate cells

Identifiers

PMID42337536
PMCPMC13325598

What Socratic holds

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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 Socratic graph.