| Title | Autophagy loss impedes cancer-associated fibroblast activation via downregulating proline biosynthesis |
| Authors | Bai, Jingru Liu, Tong Tu, Bo Yuan, Meng Shu, Zhaoqi Fan, Minghe Huo, Sihan Guo, Yuyao Wang, Lina Wang, Hua Zhao, Ying |
| Affiliation | Peking Univ, Hlth Sci Ctr, Beijing Key Lab Prot Posttranslat Modificat & Cel, Dept Biochem & Mol Biol,Sch Basic Med Sci, Beijing, Peoples R China Shenzhen Univ, Sch Med, Marshall Lab Biomed Engn, Hong Kong, Peoples R China Peking Univ Third Hosp, Inst Med Innovat & Res, Beijing, Peoples R China Fred Hutchinson Canc Res Ctr, Clin Res Div, 1124 Columbia St, Seattle, WA 98104 USA Peking Univ, Peking Univ Third Hosp, Hlth Sci Ctr, Dept Pathol,Sch Basic Med Sci, Beijing, Peoples R China |
| Keywords | PANCREATIC STELLATE CELLS TUMORS MITOCHONDRIA GENERATION GROWTH KRAS |
| Issue Date | Jul-2022 |
| Publisher | AUTOPHAGY |
| Abstract | Cancer-associated fibroblasts (CAFs) are considered one of the most critical stromal cells that interact with pancreatic ductal adenocarcinoma (PDAC) and promote tumor growth, metastasis, and treatment resistance. Previous studies illustrated macroautophagy/autophagy contributes to CAF activation during tumor progression. Here in our study, we found that autophagy deficiency in CAFs impedes CAF activation by inhibiting proline biosynthesis and collagen production. Furthermore, we uncovered that autophagy promotes proline biosynthesis through mitophagy-mediated regulation of NADK2 (NAD kinase 2, mitochondrial), an enzyme responsible for production of mitochondrial NADP(H). Using an orthotopic mouse model of PDAC, we found that inhibiting mitophagy by targeting PRKN (parkin RBR E3 ubiquitin protein ligase) in the stroma reduced tumor weight. Thus, inhibition of CAFs mitophagy might be an attractive strategy for stroma-focused anti-cancer intervention. |
| URI | http://hdl.handle.net/20.500.11897/649072 |
| ISSN | 1554-8627 |
| DOI | 10.1080/15548627.2022.2093026 |
| Indexed | SCI(E) |
| Appears in Collections: | 第三医院 |
