Evidence map›Paper›PMID 41257838›Full record

ArticleNature communications2025

A moonlighting function of tumoral interleukin-1β precursor promotes metastasis via RACK1-mediated actin remodeling.

Quanzhu Chen, Pan Wu, Jing Cai, Xingxing Lu, Zhaojian Gong, Pan Chen, Zhaoyang Zeng, Guiyuan Li, Wei Xiong, Mei Yi and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
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.

Quanzhu Chen *NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Pan Wu *NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Jing CaiDepartment of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Xingxing LuNHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Zhaojian GongDepartment of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.ORCID http://orcid.org/0000-0001-7501-3613
Pan ChenNHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Zhaoyang ZengNHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.ORCID http://orcid.org/0000-0002-0648-0565
Guiyuan LiNHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Wei XiongNHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.ORCID http://orcid.org/0000-0003-1635-8173
Mei YiFuRong Laboratory, Changsha, Hunan, China. yi_mei@csu.edu.cn.
Bo XiangNHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China. xiangbolin@csu.edu.cn.ORCID http://orcid.org/0000-0003-2641-5434

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Interleukin-1β (IL-1β) is a key inflammatory mediator in cancer. Its precursor, Pro-IL-1β, is conventionally considered inactive. Here we demonstrate that head and neck squamous cell carcinoma (HNSCC) cells exhibit significantly elevated Pro-IL-1β expression, driven by super-enhancer-mediated transcription of the IL1B gene. We show that intracellular Pro-IL-1β promotes tumor invasion and metastasis independent of IL-1β processing. Mechanistically, Pro-IL-1β binds RACK1 and inhibits its UBE2T-mediated ubiquitination, thereby stabilizing RACK1 and activating RhoA signaling to induce actin cytoskeleton remodeling and pseudopodia formation. Genetic inhibition of RACK1 abolishes Pro-IL-1β-induced metastasis. Clinically, RACK1 protein levels correlate with Pro-IL-1β expression in HNSCC specimens. Furthermore, we identify the natural compound Q3MG as a direct binder of Pro-IL-1β; it promotes lysosomal degradation of Pro-IL-1β and suppresses metastatic progression both in vitro and in vivo. Our study reveals a non-canonical, moonlighting function of Pro-IL-1β in tumor progression and highlights Q3MG as a promising therapeutic agent against metastatic cancer.

Indexed as

ActinsHead and Neck NeoplasmsInterleukin-1betaNeoplasm ProteinsReceptors for Activated C KinaseSquamous Cell Carcinoma of Head and NeckAnimalsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMiceNeoplasm InvasivenessNeoplasm MetastasisrhoA GTP-Binding ProteinSignal TransductionActinsIL1B protein, humanInterleukin-1betaNeoplasm ProteinsRACK1 protein, humanReceptors for Activated C KinaserhoA GTP-Binding ProteinUbiquitin-Conjugating Enzymes

Identifiers

PMID41257838
PMCPMC12630722

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.