Title | The Lin28b/Wnt5a axis drives pancreas cancer through crosstalk between cancer associated fibroblasts and tumor epithelium |
Authors | Shu, Zhaoqi Fan, Minghe Tu, Bo Tang, Zhiheng Wang, Haojie Li, Haimeng Li, Hengchao Yuan, Meng Bai, Jingru Huo, Sihan Wang, Lina Zhu, Wei-Guo Wang, Wei Liu, Xiaoyun Shu, Shaokun Zhao, Ying |
Affiliation | Peking Univ Hlth Sci Ctr, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing Key Lab Prot Posttranslat Modificat & Cell, Beijing 100191, Peoples R China Peking Univ, Hlth Sci Ctr, Int Canc Inst, Beijing 100191, Peoples R China Univ Texas MD Anderson Canc Ctr, Mol & Cellular Oncol Dept, Houston, TX USA Fred Hutchinson Canc Ctr, Clin Res Div, Seattle, WA 98109 USA Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Microbiol, Beijing, Peoples R China Peking Univ Hlth Sci Ctr, Ctr Precis Med Multi Om Res, Sch Basic Med Sci, Beijing, Peoples R China Peking Univ Canc Hosp & Inst, Beijing, Peoples R China FuDan Univ, Huashan Hosp, Inst Pancreat Dis, Dept Pancreat Surg, Shanghai 200040, Peoples R China Shenzhen Univ, Sch Med, Marshall Lab Biomed Engn, Shenzhen 518055, Peoples R China Shenzhen Univ, Sch Med, Dept Biochem & Mol Biol, Shenzhen, Peoples R China Peking Univ, Sch Basic Med Sci, Dept Immunol, NHC Key Lab Med Immunol, Beijing, Peoples R China |
Keywords | TGF-BETA SUBTYPES WNT5A EXPRESSION KRAS |
Issue Date | 28-Oct-2023 |
Publisher | NATURE COMMUNICATIONS |
Abstract | Bidirectional signal transduction between tumor epithelial cells and tumor microenvironment (TME) is important for tumor development. Here we show that Lin28b/let-7 pathway is indispensable for modulating the expression of Wnt5a in tumor epithelium, which could be secreted and then up-regulates Lin28b in cancer-associated fibroblasts (CAFs). Moreover, we demonstrate that Lin28b in CAFs promoted growth of PDAC by inducing cytokine PCSK9's production. Using an orthotopic mousemodel of PDAC, we find that depletion of Lin28b in CAFs reduced tumor weight, highlighting the importance of Lin28b in PDAC stroma. Thus, our study shows that the Lin28b-Wnt5a axis plays a critical role in bidirectional crosstalk between pancreatic tumor epithelium and TME and results in a pro-tumorigenic contexture. |
URI | http://hdl.handle.net/20.500.11897/691187 |
DOI | 10.1038/s41467-023-42508-8 |
Indexed | SCI(E) |
Appears in Collections: | 北京肿瘤医院 基础医学院 |