Related Experiment Video
Updated: Aug 6, 2026
11:27
Modeling Spontaneous Metastatic Renal Cell Carcinoma (mRCC) in Mice Following Nephrectomy
Published on: April 29, 2014
mTORC1 activation induces B7-H3-dependent metabolic reprogramming in renal cell carcinoma (RCC)
Keying Li1, Heng Du2,3, Yifan Wang1
1Department 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.
Oncogene
|July 20, 2026
Summary
Researchers identified B7-H3 as a key driver in Tsc2-deficient renal cell carcinoma (RCC). Deleting B7-H3 suppressed tumor growth and restored normal metabolism, highlighting its potential as a therapeutic target for TSC-associated kidney tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Renal cell carcinoma (RCC) is a major cause of cancer mortality worldwide.
- Aberrant mTORC1 pathway activation is common in RCC, but its role in tumor development is unclear.
- Lack of adequate animal models hinders research into RCC mechanisms and targeted therapies.
Purpose of the Study:
- To investigate the mechanisms of mTORC1-driven renal cell carcinoma using a novel mouse model.
- To identify molecular drivers and potential therapeutic targets in Tsc2-deficient RCC.
- To characterize the role of B7-H3 in chromophobe renal cell carcinoma (ChRCC) development and progression.
Main Methods:
- Single-cell transcriptomic, proteomic, and metabolomic profiling of kidneys from embryonic Tsc2-deleted mice.
- Analysis of tumor cell populations, including gene and protein expression.
- Investigating the functional role of B7-H3 through gene deletion studies in mice.
- Correlation analysis of B7-H3 expression with clinical markers in human ChRCC specimens.
Main Results:
- A distinct tumor cell population with intercalated cell signatures and hyperactivated mTORC1 was identified, resembling human ChRCC.
- Upregulation of the immune checkpoint molecule B7-H3 was observed, driven by the transcription factor NRF1.
- B7-H3 expression correlates with hallmark ChRCC markers in human tumors.
- B7-H3 deletion in mice suppressed Tsc2 loss-driven tumor formation, normalized amino acid metabolism, and reduced proteasome activity.
Conclusions:
- B7-H3 is a functional driver of Tsc2-mediated ChRCC.
- B7-H3 is a promising therapeutic target for TSC-associated renal tumors.
- This study provides a novel model for investigating ChRCC pathogenesis and therapeutic strategies.
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