转移
癌症研究
癌症
细胞迁移
线粒体
化学
免疫学
生物
细胞生物学
医学
内科学
细胞
生物化学
作者
Shuyu Fu,Hui Deng,Irene Bertolini,Michela Perego,Eric S. Chen,Emilio Sanseviero,Ali Mostafa,Kevin Alicea-Torres,Laura Garcia-Gerique,Erica L. Stone,Andrew V. Kossenkov,Zachary T. Schug,Brian Nam,Charles Mulligan,Dario C. Altieri,Yulia Nefedova,Dmitry I. Gabrilovich
出处
期刊:Cancer immunology research
[American Association for Cancer Research]
日期:2022-12-22
卷期号:11 (3): 278-289
标识
DOI:10.1158/2326-6066.cir-22-0035
摘要
Pathologically activated neutrophils (PMN) with immunosuppressive activity, which are termed myeloid-derived suppressor cells (PMN-MDSC), play a critical role in regulating tumor progression. These cells have been implicated in promoting tumor metastases by contributing to premetastatic niche formation. This effect was facilitated by enhanced spontaneous migration of PMN from bone marrow to the premetastatic niches during the early-stage of cancer development. The molecular mechanisms underpinning this phenomenon remained unclear. In this study, we found that syntaphilin (SNPH), a cytoskeletal protein previously known for anchoring mitochondria to the microtubule in neurons and tumor cells, could regulate migration of PMN. Expression of SNPH was decreased in PMN from tumor-bearing mice and patients with cancer as compared with PMN from tumor-free mice and healthy donors, respectively. In Snph-knockout (SNPH-KO) mice, spontaneous migration of PMN was increased and the mice showed increased metastasis. Mechanistically, in SNPH-KO mice, the speed and distance travelled by mitochondria in PMN was increased, rates of oxidative phosphorylation and glycolysis were elevated, and generation of adenosine was increased. Thus, our study reveals a molecular mechanism regulating increased migratory activity of PMN during cancer progression and suggests a novel therapeutic targeting opportunity.
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