White-to-brown adipose switching promotes bladder cancer progression
Mingchao Gao1, Chunni Li2, Wenjie Li1
1Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Guangzhou, Guangdong, 510120, China; Guangdong Provincial Clinical Research Center for Urological Diseases, Guangdong 510120, China.
Neoplasia (New York, N.Y.)
|February 14, 2026
Summary
Bladder cancer cells release parathyroid hormone-related protein (PTHrP), promoting adipose tissue browning. This process fuels cancer progression via free fatty acid uptake and metabolic reprogramming, offering a new therapeutic target.
Area of Science:
- Oncology
- Metabolic Research
- Cell Biology
Background:
- Bladder cancer invasion into surrounding fat worsens outcomes.
- Mechanisms of cancer-adipose tissue communication are unclear.
Purpose of the Study:
- To elucidate the molecular crosstalk between bladder cancer and perivesical adipose tissue.
- To identify key signaling pathways involved in this interaction.
Main Methods:
- Systematic characterization of bidirectional regulatory networks.
- In vitro studies on cancer cell-adipocyte co-culture.
- In vivo experiments using PKA inhibitor (H89).
Main Results:
- Bladder cancer cells secrete PTHrP, inducing adipose tissue browning via PKA signaling.
- Adipose tissue browning releases free fatty acids, enhancing cancer cell proliferation, invasion, and metastasis.
- PKA inhibition (H89) reversed browning and attenuated tumor progression in vivo.
Conclusions:
- PTHrP drives adipose tissue browning, accelerating bladder cancer progression.
- This cancer-adipose tissue crosstalk represents a novel therapeutic target for bladder cancer intervention.
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