| Title | Cancer-associated fibroblasts employ NUFIP1-dependent autophagy to secrete nucleosides and support pancreatic tumor growth |
| Authors | Yuan, Meng Tu, Bo Li, Hengchao Pang, Huanhuan Zhang, Nan Fan, Minghe Bai, Jingru Wang, Wei Shu, Zhaoqi DuFort, Christopher C. Huo, Sihan Zhai, Jie Yao, Ke Wang, Lina Ying, Haoqiang Zhu, Wei-Guo Fu, Deliang Hu, Zeping Zhao, Ying |
| Affiliation | Peking Univ Hlth Sci Ctr, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing Key Lab Prot Posttranslat Modificat & Cel, Beijing, Peoples R China Shenzhen Univ, Marshall Lab Biomed Engn, Sch Med, Shenzhen, Peoples R China Univ Texas MD Anderson Canc Ctr, Mol & Cellular Oncol Dept, Houston, TX 77030 USA Fred Hutchinson Canc Res Ctr, Clin Res Div, 1124 Columbia St, Seattle, WA 98104 USA FuDan Univ, Huashan Hosp, Inst Pancreat Dis, Dept Pancreat Surg, Shanghai, Peoples R China Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Beijing Frontier Res Ctr Biol Struct, Sch Pharmaceut Sci, Beijing, Peoples R China Peking Univ, Sch Basic Med Sci, Dept Immunol, NHC Key Lab Med Immunol, Beijing, Peoples R China Shenzhen Univ, Sch Med, Dept Biochem & Mol Biol, Shenzhen, Peoples R China |
| Keywords | GLUTAMINE-SYNTHETASE STELLATE CELLS MYC KRAS DEFICIENCY METABOLISM MAINTAINS PROTEIN |
| Issue Date | Aug-2022 |
| Publisher | NATURE CANCER |
| Abstract | Yuan et al. demonstrate that cancer-associated fibroblasts in the pancreatic tumor microenvironment secrete nucleosides through autophagy in an NUFIP1-dependent manner, thereby inducing glucose consumption under glutamine-deprived conditions and promoting tumor growth. Cancer-associated fibroblasts (CAFs) are one of the most prominent and active components in the pancreatic tumor microenvironment. Our data show that CAFs are critical for survival from pancreatic ductal adenocarcinoma (PDAC) on glutamine deprivation. Specifically, we uncovered a role for nucleosides, which are secreted by CAFs through autophagy in a nuclear fragile X mental retardation-interacting protein 1 (NUFIP1)-dependent manner, increased glucose utilization and promoted growth of PDAC. Moreover, we demonstrate that CAF-derived nucleosides induced glucose consumption under glutamine-deprived conditions and displayed a dependence on MYC. Using an orthotopic mouse model of PDAC, we found that inhibiting nucleoside secretion by targeting NUFIP1 in the stroma reduced tumor weight. This finding highlights a previously unappreciated metabolic network within pancreatic tumors in which diverse nutrients are used to promote growth in an austere tumor microenvironment. |
| URI | http://hdl.handle.net/20.500.11897/650655 |
| DOI | 10.1038/s43018-022-00426-6 |
| Indexed | SCI(E) |
| Appears in Collections: | 基础医学院 |
