Evidence map›Paper›PMID 42477460›Full record

ArticleOncogene2026

mTORC1 activation induces B7-H3-dependent metabolic reprogramming in renal cell carcinoma (RCC).

Keying Li, Heng Du, Yifan Wang, Damir Khabibullin, Michel Alchoueiry, Melissa Daou, John M Asara, David J Kwiatkowski, Elizabeth P Henske, Heng-Jia Liu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 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

10 authors.

Keying Li *Department of Colorectal Surgery of Sir Run Run Shaw Hospital, and Centre for Infection, Immunity and Cancer of Zhejiang University-University of Edinburgh Institute (ZJE), Zhejiang University School of Medicine, Zhejiang University, Hangzhou, PR China.ORCID http://orcid.org/0009-0009-1561-7605
Heng Du *Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, PR China.
Yifan WangDepartment of Colorectal Surgery of Sir Run Run Shaw Hospital, and Centre for Infection, Immunity and Cancer of Zhejiang University-University of Edinburgh Institute (ZJE), Zhejiang University School of Medicine, Zhejiang University, Hangzhou, PR China.ORCID http://orcid.org/0009-0002-2801-604X
Damir KhabibullinPulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Michel AlchoueiryPulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-8288-7212
Melissa DaouPulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
John M AsaraDivision of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA, USA.
David J KwiatkowskiPulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Elizabeth P HenskePulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. ehenske@bwh.harvard.edu.ORCID http://orcid.org/0000-0001-7978-6699
Heng-Jia LiuDepartment of Colorectal Surgery of Sir Run Run Shaw Hospital, and Centre for Infection, Immunity and Cancer of Zhejiang University-University of Edinburgh Institute (ZJE), Zhejiang University School of Medicine, Zhejiang University, Hangzhou, PR China. hengjialiu@intl.zju.edu.cn.ORCID http://orcid.org/0000-0001-9685-6572

Funding

Mechanisms of immunosuppression in the development and progression of renal disease in Tuberous Sclerosis ComplexR01DK133243 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI Elizabeth P Henske · 2023 to 2026
$2.1M
NIDDK NIH HHS R01 DK133243
6 · The paper itself

Abstract

Renal cell carcinoma (RCC) affects over 435,000 people worldwide each year and remains a significant cause of cancer mortality. Aberrant activation of pathways such as mTORC1 is frequently observed in RCC, yet the mechanisms by which mTORC1 contributes to tumor development remain poorly understood. The lack of suitable animal models has limited progress in uncovering these mechanisms and advancing targeted treatments. Here, we performed single-cell transcriptomic, proteomic, and metabolomic profiling of kidneys from mice with embryonic Tsc2 deletion at E17.5, which revealed a distinct tumor cell population characterized by intercalated cell signatures, co-expression of Foxi1 and Rhcg, and hyperactivated mTORC1. These lesions closely resemble human chromophobe renal cell carcinoma (ChRCC), a subtype of RCC. The tumors show marked upregulation of the immune checkpoint molecule B7-H3. Mechanistically, the transcription factor NRF1 is elevated in Tsc2-deficient lesions and drives B7-H3 expression in tumor cells. In human specimens, B7-H3 is broadly expressed in both classical and sarcomatoid ChRCC and correlates with hallmark markers FOXI1, MUC2, and HEPACAM2. Strikingly, B7-H3 deletion in mice suppresses Tsc2 loss-driven cystic and tumor formation, restores amino acid metabolism, and attenuates aminoacyl-tRNA biosynthesis and proteasome activity. Collectively, these findings identify B7-H3 as a functional driver of Tsc2-mediated ChRCC and a promising therapeutic target in TSC-associated renal tumors.

Indexed as

Carcinoma, Renal CellKidney NeoplasmsMechanistic Target of Rapamycin Complex 1AnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansMetabolic ReprogrammingMiceTuberous Sclerosis Complex 2 ProteinMechanistic Target of Rapamycin Complex 1TSC2 protein, humanTsc2 protein, mouseTuberous Sclerosis Complex 2 Protein

Identifiers

PMID42477460
PMCPMC13481258

What OpenQuestion 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 OpenQuestion graph.