IGFBP1 Sustains Cell Survival during Spatially-Confined Migration and Promotes Tumor Metastasis

被引：11
|
作者：
Cai, Guoqing [1 ]
Qi, Yijun [2 ]
Wei, Ping [3 ]
Gao, Hong [1 ]
Xu, Chenqi [2 ,4 ]
Zhao, Yun [1 ,2 ]
Qu, Xiujuan [5 ]
Yao, Feng [6 ]
Yang, Weiwei [1 ,2 ]
机构：
[1] Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Ctr Excellence Mol Cell Sci,State Key Lab Cell Bio, Shanghai 200031, Peoples R China
[2] Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Life Sci, Key Lab Syst Hlth Sci Zhejiang Prov, Hangzhou 310024, Peoples R China
[3] Fudan Univ, Shanghai Canc Ctr, Dept Pathol, Shanghai 200032, Peoples R China
[4] Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Shanghai Sci Res Ctr, CAS Ctr Excellence Mol Cell Sci,State Key Lab Mol, Shanghai 200031, Peoples R China
[5] China Med Univ, Hosp 1, Dept Med Oncol, Shenyang 110001, Peoples R China
[6] Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Sch Med, Dept Thorac Surg, Shanghai 200031, Peoples R China
来源：
ADVANCED SCIENCE | 2023年 / 10卷 / 21期
基金：
国家重点研发计划; 中国国家自然科学基金;
关键词：
confined migration; insulin-like growth factor-binding protein 1; mitochondrial reactive oxygen species; superoxide dismutase; tumor metastasis; MANGANESE SUPEROXIDE-DISMUTASE; BREAST-CANCER; BINDING PROTEIN-1; GROWTH; OXYGEN; EXPRESSION; INVASION; SOD2; AKT; ROS;
D O I：
10.1002/advs.202206540
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
Cell migration is a pivotal step in metastatic process, which requires cancer cells to navigate a complex spatially-confined environment, including tracks within blood vessels and in the vasculature of target organs. Here it is shown that during spatially-confined migration, the expression of insulin-like growth factor-binding protein 1 (IGFBP1) is upregulated in tumor cells. Secreted IGFBP1 inhibits AKT1-mediated phosphorylation of mitochondrial superoxide dismutase (SOD2) serine (S) 27 and enhances SOD2 activity. Enhanced SOD2 attenuates mitochondrial reactive oxygen species (ROS) accumulation in confined cells, which supports tumor cell survival in blood vessels of lung tissues, thereby accelerating tumor metastasis in mice. The levels of blood IGFBP1 correlate with metastatic recurrence of lung cancer patients. This finding reveals a unique mechanism by which IGFBP1 sustains cell survival during confined migration by enhancing mitochondrial ROS detoxification, thereby promoting tumor metastasis.
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页数：17
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