Evidence map›Paper›PMID 39763264›Full record

ArticleJournal of cellular physiology2025

SMAD4 Regulates the Expression of LCK Affecting Chimeric Antigen Receptor-T Cells Proliferation Through PI3K/Akt Signaling Pathway.

Rongxue Wan, Bowen Fu, Xiaokang Fu, Zengping Liu, Nafeisha Simayi, Yongshui Fu, Huaqin Liang, Chengyao Li, Wenhua Huang

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of cellular physiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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. CD147 regulates CD8iScience · 2026
    Article
  3. Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Rongxue WanDepartment of Transfusion Medicine, School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.ORCID 0000-0003-2048-0665
Bowen FuGuangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Xiaokang FuGuangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.ORCID 0000-0003-1070-8021
Zengping LiuGuangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Nafeisha SimayiGuangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Yongshui FuDepartment of Transfusion Medicine, School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
Huaqin LiangGuangzhou Blood Center, Institute of Blood Transfusion and Hematology, Guangzhou Medical University, Guangzhou, Guangdong, China.
Chengyao LiDepartment of Transfusion Medicine, School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
Wenhua HuangGuangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

Funding

This research was funded by the National Natural Science Foundation of China (NO.82101930, to Rongxue Wan), China Postdoctoral Science Foundation (NO.2023M741558, to Rongxue Wan), China postdoctoral Science Foundation Special Fund (NO.2024T170389, to Rongxue Wan), Science and Technology Projects in Guangzhou (2023A03J0552, to Yongshui Fu).
6 · The paper itself

Abstract

The proliferation of CAR-T cells was hindered and cannot play its killing function well in solid tumors. And yet the regulatory mechanism of CAR-T cell proliferation is not fully understood. Here, we showed that recombinant expression of CD19CAR in T cells significantly increased the basal activation level of CAR-T cells and LCK activation. Both LCK and SMAD4 were essential for CAR-T cells proliferation since over-express LCK or SMAD4 significantly promotes CAR-T cells proliferation, while knock-down LCK or SMAD4 expression inhibited the proliferation of CAR-T cells seriously. More cells go into apoptosis when knock-down LCK or SMAD4 expression, and the cell cycle was arrested in G2/M or S phase, respectively. Over-express LCK or SMAD4 significantly promotes phosphorylation of PI3K and Akt, while it was inhibited when cells were treated with PI3K and Akt inhibitors (LY294002 or MK2206). Further mechanism exploration experiments showed that SMAD4 bound on the promoter region of LCK regulating its expression. Taken together, we reported that the transcription factor SMAD4 regulated the expression of LCK and further involved in the PI3K/Akt signaling pathway to affect the proliferation of CAR-T cells.

Indexed as

Cell ProliferationLymphocyte Specific Protein Tyrosine Kinase p56(lck)Phosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReceptors, Chimeric AntigenSignal TransductionSmad4 ProteinApoptosisHumansLymphocyte ActivationPhosphorylationT-LymphocytesLCK protein, humanLymphocyte Specific Protein Tyrosine Kinase p56(lck)Phosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReceptors, Chimeric AntigenSmad4 ProteinSMAD4 protein, humanAktCAR‐T cell therapyLCKproliferationSMAD4

Identifiers

PMID39763264
PMCPMC11704455

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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.