机构：[1]Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China[2]Department of Genetics, Harvard Medical School, Boston, MA 02115, USA[3]Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA[4]Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, Turkey[5]Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Boston, MA 02115, USA[6]Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China普通外科首都医科大学宣武医院[7]Howard Hughes Medical Institute, Boston, MA 02115, USA
Interactions between tumors and host tissues play essential roles in tumor-induced systemic wasting and cancer cachexia, including muscle wasting and lipid loss. However, the pathogenic molecular mechanisms of wasting are still poorly understood. Using a fly model of tumor-induced organ wasting, we observed aberrant MEK activation in both tumors and host tissues of flies bearing gut-yki(3SA) tumors. We found that host MEK activation results in muscle wasting and lipid loss, while tumor MEK activation is required for tumor growth. Strikingly, host MEK suppression alone is sufficient to abolish the wasting phenotypes without affecting tumor growth. We further uncovered that yki(3SA) tumors produce the vein (vn) ligand to trigger autonomous Egfr/MEK-induced tumor growth and produce the PDGF- and VEGF-related factor 1 (Pvf1) ligand to non-autonomously activate host Pvr/MEK signaling and wasting. Altogether, our results demonstrate the essential roles and molecular mechanisms of differential MEK activation in tumor-induced host wasting.
基金：
American Diabetes Association [1-16-PDF-108]; NIH [R01AR057352, P01CA120964]
第一作者机构：[1]Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China[2]Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
通讯作者：
通讯机构：[1]Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China[2]Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
推荐引用方式(GB/T 7714)：
Wei Song ,Serkan Kir ,Shangyu Hong ,et al.Tumor-Derived Ligands Trigger Tumor Growth and Host Wasting via Differential MEK Activation[J].DEVELOPMENTAL CELL.2019,48(2):277-+.doi:10.1016/j.devcel.2018.12.003.
APA：
Wei Song,,Serkan Kir,,Shangyu Hong,,Yanhui Hu,,Xiaohui Wang,...&Norbert Perrimon.(2019).Tumor-Derived Ligands Trigger Tumor Growth and Host Wasting via Differential MEK Activation.DEVELOPMENTAL CELL,48,(2)
MLA：
Wei Song,,et al."Tumor-Derived Ligands Trigger Tumor Growth and Host Wasting via Differential MEK Activation".DEVELOPMENTAL CELL 48..2(2019):277-+
生物