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IGFBP1 在空间受限迁移过程中维持细胞存活并促进肿瘤转移。

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

机构信息

State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.

Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China.

出版信息

Adv Sci (Weinh). 2023 Jul;10(21):e2206540. doi: 10.1002/advs.202206540. Epub 2023 Jun 9.

DOI:10.1002/advs.202206540
PMID:37296072
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10375137/
Abstract

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.

摘要

细胞迁移是转移过程中的关键步骤，需要癌细胞在复杂的空间受限环境中导航，包括血管内和靶器官血管中的轨迹。研究表明，在空间受限迁移过程中，肿瘤细胞中胰岛素样生长因子结合蛋白 1（IGFBP1）的表达上调。分泌的 IGFBP1 抑制 AKT1 介导的线粒体超氧化物歧化酶（SOD2）丝氨酸（S）27 的磷酸化，并增强 SOD2 的活性。增强的 SOD2 减轻了受限细胞中线粒体活性氧（ROS）的积累，这支持了肿瘤细胞在肺组织血管中的存活，从而加速了小鼠的肿瘤转移。血液 IGFBP1 的水平与肺癌患者转移复发相关。这一发现揭示了一种独特的机制，即 IGFBP1 通过增强线粒体 ROS 解毒作用来维持细胞在受限迁移过程中的存活，从而促进肿瘤转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10375137/07ba980cd8ac/ADVS-10-2206540-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10375137/a607b5b8ee01/ADVS-10-2206540-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10375137/16670f1b9c37/ADVS-10-2206540-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10375137/94b1978661c1/ADVS-10-2206540-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10375137/1007d8c42c20/ADVS-10-2206540-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10375137/38d02910eafd/ADVS-10-2206540-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10375137/731bdd71dfb0/ADVS-10-2206540-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10375137/828868c809c2/ADVS-10-2206540-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10375137/07ba980cd8ac/ADVS-10-2206540-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10375137/a607b5b8ee01/ADVS-10-2206540-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10375137/16670f1b9c37/ADVS-10-2206540-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10375137/94b1978661c1/ADVS-10-2206540-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10375137/1007d8c42c20/ADVS-10-2206540-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10375137/38d02910eafd/ADVS-10-2206540-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10375137/731bdd71dfb0/ADVS-10-2206540-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10375137/828868c809c2/ADVS-10-2206540-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10375137/07ba980cd8ac/ADVS-10-2206540-g006.jpg

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