期刊
NATURE
卷 608, 期 7922, 页码 421-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41586-022-05030-3
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资金
- National Program on Key Research [2021YFA0804700]
- Program for Professor of Special Appointment in Shanghai (Eastern Scholar) [TP2018007]
- Scandinavia-Japan Sasakawa Foundation
- Karolinska Institute Foundation
- Japan Society for the Promotion of Science (JSPS) Overseas Research Fellowships
- European Research Council (ERC) advanced grant ANGIOFAT [250021]
- Swedish Research Council
- Swedish Cancer Foundation
- Swedish Children's Cancer Foundation
- Strategic Research Areas (SFO)-Stem Cell and Regenerative Medicine Foundation
- Karolinska Institute distinguished professor award
- Torsten Soderbergs Foundation
- Maud and Birger Gustavsson Foundation
- NOVO Nordisk Foundation-Advance grant
- NOVO Nordisk Foundation
- Knut and Alice Wallenberg's Foundation
Exposure to cold conditions inhibits the growth of various types of solid tumors by decreasing blood glucose and impeding glycolysis-based metabolism in cancer cells. Cold exposure also reduces glucose uptake in tumor tissue. These findings provide a new concept and paradigm for cancer therapy using a simple and effective approach.
Glucose uptake is essential for cancer glycolysis and is involved in non-shivering thermogenesis of adipose tissues(1,6). Most cancers use glycolysisto harness energy for their infinite growth, invasion and metastasis(2,7,8). Activation of thermogenic metabolism in brown adipose tissue (BAT) by cold and drugs instigates blood glucose uptake in adipocytes(4,5,9). However, the functional effects of the global metabolic changes associated with BAT activation on tumour growth are unclear. Here we show that exposure of tumour-bearing mice to cold conditions markedly inhibits the growth of various types of solid tumours, including clinically untreatable cancers such as pancreatic cancers. Mechanistically, cold-induced BAT activation substantially decreases blood glucose and impedes the glycolysis-based metabolism in cancer cells. The removal of BAT and feeding on a high-glucose diet under cold exposure restore tumour growth, and genetic deletion of Ucp1-the key mediator for BAT-thermogenesis-ablates the cold-triggered anticancer effect. In a pilot human study, mild cold exposure activates a substantial amount of BAT in both healthy humans and a patient with cancer with mitigated glucose uptake in the tumour tissue. These findings provide a previously undescribed concept and paradigm for cancer therapy that uses a simple and effective approach. We anticipate that cold exposure and activation of BAT through any other approach, such as drugs and devices either alone or in combination with other anticancer therapeutics, will provide a general approach for the effective treatment of various cancers.
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