Lipid metabolism in adipocytes modulates tumor growth at a distance through Nplp2-mediated Wnt5 signal
Abstract
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (18)
Chen Yang
Hangzhou Institute of Advanced Studies
Yang Yang
Zheng Liu
Xinpeng Bai
Division of Life Science, The Hong Kong University of Science and Technology
Xiaohui Ma
Division of Life Science, The Hong Kong University of Science and Technology
Jihong Tang
Division of Life Science, The Hong Kong University of Science and Technology
Rui Huang
School of Chemistry
Yuanyuan Liao
Division of Life Science, The Hong Kong University of Science and Technology
Yang Liu
Lu Wen
Cancer Center, Hubei Key Laboratory of Precision Radiation Oncology, Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of science and Technology
Min Liu
Alan Jian Zhu
School of Life Sciences, Peking University
Cong Yu
State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Centre for New Organic Matter, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, School of Medicine, and Frontiers Science Centre for Cell Responses
Yusong Guo
Jiguang Wang
Division of Life Science, The Hong Kong University of Science and Technology
Xiang David Li
Department of Chemistry, The University of Hong Kong
Toyotaka Ishibashi
Division of Life Science, The Hong Kong University of Science and Technology
Yan Yan