Evidence map›Paper›PMID 42199156›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

mTORC2 Phosphorylation of GSDME-N Drives Cullin4B-Mediated Proteasomal Degradation to Suppress Pyroptosis and Confer Radioresistance in Small Cell Lung Cancer.

Qing-Qing Xu, Ci-Ming Sun, Sui-Xian Zhang, Rui Li, Chen-Fei Wu, Zai-Shan Lin, Li Li, Run-Zhe Chen, Qi-Wen Li, Yuan-Yuan Chen and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

12 authors.

Qing-Qing XuState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China.
Ci-Ming SunState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China.
Sui-Xian ZhangState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China.
Rui LiState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China.
Chen-Fei WuState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China.
Zai-Shan LinState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China.
Li LiState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China.
Run-Zhe ChenState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China.
Qi-Wen LiState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China.
Yuan-Yuan ChenState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China.ORCID https://orcid.org/0000-0002-1611-0111
Xuan LiState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China.ORCID https://orcid.org/0000-0001-5744-5818
Ming ChenState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China.ORCID https://orcid.org/0000-0001-5041-9342

Funding

Cancer Innovative Research Program PT13030302Clinical Research 5010 Program 202208Guangzhou Science and Technology Basic and Applied Basic Research Project SL2022A04J01961Natural Science Foundation of China 82202827Natural Science Foundation of China 82272744Natural Science Foundation of China 82303693Natural Science Foundation of Guangdong Province 2022A1515010814Noncommunicable Chronic Diseases-National Science and Technology Major Project 2023ZD0502100
6 · The paper itself

Abstract

Radioresistance is a main reason for treatment failure in patients with small cell lung cancer (SCLC). Consequently, it is important to determine the key mechanism and explore effective strategies to prevent SCLC radioresistance. We use an unbiased CRISPR screen to identify GSDME, a member of the Gasdermin (GSDM) family, as a critical driver of radiosensitivity in SCLC. Furthermore, we identify mTORC2 facilitates SCLC radioresistance by inhibiting GSDME-N-mediated pyroptosis. Mechanistically, mTORC2 phosphorylates GSDME-N at serine 114 (S114), promoting the recruitment of the CUL4B-RBBP4 E3 ubiquitin ligase complex. This complex mediates K48-linked ubiquitination of GSDME-N at lysine 41 (K41), leading to its proteasomal degradation. Clinically, elevated mTORC2 is linked to an unfavorable prognosis in SCLC patients. The study reveals mTORC2 phosphorylates GSDME-N and promotes its Cullin4B-mediated proteasomal degradation to suppress pyroptosis and drive radioresistance in SCLC.

Indexed as

Cullin ProteinsLung NeoplasmsMechanistic Target of Rapamycin Complex 2PyroptosisRadiation ToleranceSmall Cell Lung CarcinomaAnimalsCell Line, TumorHumansMicePhosphorylationProteasome Endopeptidase ComplexCUL4B protein, humanCullin ProteinsMechanistic Target of Rapamycin Complex 2Proteasome Endopeptidase ComplexGSDMEmTORC2pyroptosisradioresistancesmall cell lung cancer

Identifiers

PMID42199156
PMCPMC13335795

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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.