Lipid metabolism in adipocytes modulates tumor growth at a distance through Nplp2-mediated Wnt5 signal

• 成果类型: Article
• 署名作者: Yang, Chen; Yang, Yang; Liu, Zheng; Bai, Xinpeng; Ma, Xiaohui; Tang, Jihong; Huang, Rui; Liao, Yuanyuan; Liu, Yang; Wen, Lu; Liu, Min; Zhu, Alan Jian; Yu, Cong; Guo, Yusong; Wang, Jiguang; Li, Xiang David; Ishibashi, Toyotaka; Yan, Yan
• 署名单位: Hong Kong University of Science & Technology; University of Hong Kong; Huazhong University of Science & Technology; Peking University; Southern University of Science & Technology; Southern University of Science & Technology; Hong Kong University of Science & Technology; Chinese Academy of Sciences; Hong Kong University of Science & Technology; Shenzhen Institute of Advanced Technology, CAS; Hong Kong University of Science & Technology
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2601991123
• 发表日期: 2026-05-05
• 页码: e2601991123
• 关键词: Drosophila melanogaster; Drosophila tumor model; inter-organ communication; caloric restriction; drosophila; secretion; wingless; protein; cancer; gene

摘要

The host metabolic state can potentially affect the growth trajectories of tumors growing at local sites, which are highly variable and unpredictable among populations. The molecular links between systemic metabolism and tumor growth outcomes remain largely unclear. Here, we harnessed the genetic power of the Drosophila model to perform genetic screens and identified molecular players in the adipose tissue that can change the growth trajectory of remotely growing tumors. We found that variation of triacylglycerol (TAG) metabolism state in adipocytes, which is downstream of insulin signaling regulation, can strongly change the growth trajectory of distant tumors. Mechanistically, we identified that Wnt5, which is secreted from adipocytes and transported in circulation through a population of Nplp2-lipoprotein particles, is required for distant tumor growth. Perturbation of TAG metabolism or depletion of Nplp2-lipoprotein particle formation in adipocytes reduces Wnt5 in circulation and therefore restricts distant tumor growth.