Cross, Michael, Kotschi, Stefan, Wu, Warren, Luciano-Mateo, Fedra, Kwon, Young-Yon, Dantas, Ezequiel, Niazi, Taha, Chen, Shijia, Rashidfarrokhi, Ali, Pillai, Ray, Sanford, Jack, Kim, Jeshua, Hsiang, Juliya, Gamallo-Lana, Begona, Mar, Adam C, Hao, Yuan, Rajalingam, Sahith, Huang, Annie, Shan, Jackie, Issa, Habon A, Gomez, Maria, Wang, Alice R, Zhao, Xiang, Janowitz, Tobias, White, Eileen, Liu, Yin, Wong, Kwok-Kin, Segal, Leopoldo N, Hui, Sheng, Goncalves, Marcus D, Froemke, Robert C, Papagiannakopoulos, Thales (July 2026) A dietary switch promotes sensory neuron-dependent cancer-associated cachexia. Science, 393 (6806). pp. 90-97. ISSN 0036-8075
Abstract
Sickness behaviors are common in cancer-associated cachexia and affect up to half of lung cancer patients. We demonstrate that among the most common cancer mutations, loss of liver kinase B1 (Lkb1) promotes the development of cachexia in preclinical models of lung cancer. In an effort to improve caloric intake with an obesogenic high-fat diet, we paradoxically observed worsened cachexia-associated sickness. We found that local production of prostaglandin E2 (PGE2), rather than circulating factors, promotes sickness and that genetic, dietary, and pharmacological inhibition of tumor-derived PGE2 suppresses sickness and cachexia. Notably, we demonstrate that lung sensory neuron abrogation prevents PGE2-dependent cachexia. Our study establishes localized tumor-derived signals to sensory neurons, rather than circulating factors, as drivers of cachexia and highlights a previously unknown role of the peripheral nervous system in cancer cachexia.
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders diseases & disorders > nutritional and metabolic diseases diseases & disorders > nutritional and metabolic diseases > cachexia |
| CSHL Authors: | |
| Communities: | CSHL labs > Janowitz lab CSHL Post Doctoral Fellows |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 2 July 2026 |
| Date Deposited: | 06 Jul 2026 12:32 |
| Last Modified: | 06 Jul 2026 12:32 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/42260 |
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