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成孔蛋白通过囊泡相关肌动蛋白组装促进 TGFβ 诱导的 ANGPTL4 转运、分泌和细胞侵袭。

Vesicle-Associated Actin Assembly by Formins Promotes TGFβ-Induced ANGPTL4 Trafficking, Secretion and Cell Invasion.

机构信息

Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty, University of Freiburg, 79104, Freiburg, Germany.

Deutsche Forschungsgemeinschaft Research Training Group, Membrane Plasticity in Tissue Development and Remodeling, University of Marburg, 35037, Marburg, Germany.

出版信息

Adv Sci (Weinh). 2023 Mar;10(9):e2204896. doi: 10.1002/advs.202204896. Epub 2023 Jan 24.

DOI:10.1002/advs.202204896
PMID:36691769
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10037683/
Abstract

Vesicle trafficking has emerged as an important process driving tumor progression through various mechanisms. Transforming growth factor beta (TGFβ)-mediated secretion of Angiopoietin-like 4 (ANGPTL4) is important for cancer development. Here, Formin-like 2 (FMNL2) is identified to be necessary for ANGPTL4 trafficking and secretion in response to TGFβ. Protein kinase C (PKC)-dependent phosphorylation of FMNL2 downstream of TGFβ stimulation is required for cancer cell invasion as well as ANGPTL4 vesicle trafficking and secretion. Moreover, using super resolution microscopy, ANGPTL4 trafficking is actin-dependent with FMNL2 directly polymerizing actin at ANGPTL4-containing vesicles, which are associated with Rab8a and myosin Vb. This work uncovers a formin-controlled mechanism that transiently polymerizes actin directly at intracellular vesicles to facilitate their mobility. This mechanism may be important for the regulation of cancer cell metastasis and tumor progression.

摘要

囊泡运输已成为通过多种机制推动肿瘤进展的重要过程。转化生长因子β（TGFβ）介导的血管生成素样 4（ANGPTL4）的分泌对于癌症的发展很重要。在这里，鉴定出formin 样蛋白 2（FMNL2）对于 TGFβ 刺激下 ANGPTL4 的运输和分泌是必需的。PKC 依赖性磷酸化 FMNL2 是 TGFβ 刺激后癌细胞侵袭以及 ANGPTL4 囊泡运输和分泌所必需的。此外，使用超分辨率显微镜，ANGPTL4 的运输是肌动蛋白依赖性的，FMNL2 直接在含有 ANGPTL4 的囊泡上聚合肌动蛋白，这些囊泡与 Rab8a 和肌球蛋白 Vb 相关。这项工作揭示了一个形成蛋白控制的机制，该机制可暂时将肌动蛋白直接聚合在细胞内囊泡上，以促进其迁移。这种机制可能对调节癌细胞转移和肿瘤进展很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cef/10037683/061e7fa53b9f/ADVS-10-2204896-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cef/10037683/109acda3563c/ADVS-10-2204896-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cef/10037683/6450b6e3288e/ADVS-10-2204896-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cef/10037683/be593c157492/ADVS-10-2204896-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cef/10037683/2d483eb1dd44/ADVS-10-2204896-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cef/10037683/e4805bcdb963/ADVS-10-2204896-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cef/10037683/061e7fa53b9f/ADVS-10-2204896-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cef/10037683/109acda3563c/ADVS-10-2204896-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cef/10037683/6450b6e3288e/ADVS-10-2204896-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cef/10037683/be593c157492/ADVS-10-2204896-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cef/10037683/2d483eb1dd44/ADVS-10-2204896-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cef/10037683/e4805bcdb963/ADVS-10-2204896-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cef/10037683/061e7fa53b9f/ADVS-10-2204896-g003.jpg

相似文献

[1]
Vesicle-Associated Actin Assembly by Formins Promotes TGFβ-Induced ANGPTL4 Trafficking, Secretion and Cell Invasion.

Adv Sci (Weinh). 2023-3

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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[2]
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Elife. 2024-10-31

[3]
SUN2 mediates calcium-triggered nuclear actin polymerization to cluster active RNA polymerase II.

EMBO Rep. 2024-11

[4]
The role of ncRNAs and exosomes in the development and progression of endometrial cancer.

Front Oncol. 2024-8-12

[5]
Repeated stress to the skin amplifies neutrophil infiltration in a keratin 17- and PKCα-dependent manner.

PLoS Biol. 2024-8

[6]
-Induced Angiopoietin-Like 4 Promotes Gastric Bacterial Colonization and Gastritis.

Research (Wash D C). 2024-7-17

[7]
Identification of an FMNL2 Interactome by Quantitative Mass Spectrometry.

Int J Mol Sci. 2024-5-23

[8]
Adipose-derived stem cells promote glycolysis and peritoneal metastasis via TGF-β1/SMAD3/ANGPTL4 axis in colorectal cancer.

Cell Mol Life Sci. 2024-4-21

[9]
Spatiotemporal Regulation of FMNL2 by N-Terminal Myristoylation and C-Terminal Phosphorylation Drives Rapid Filopodia Formation.

Biomolecules. 2023-3-17

本文引用的文献

[1]
Formin-Like 2 Is a Potential Biomarker of Poor Prognosis in Nasopharyngeal Carcinoma.

Oncology. 2022

[2]
Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression.

Int J Mol Sci. 2021-12-23

[3]
Small Rab GTPases in Intracellular Vesicle Trafficking: The Case of Rab3A/Raphillin-3A Complex in the Kidney.

Int J Mol Sci. 2021-7-18

[4]
ANGPTL4 overexpression is associated with progression and poor prognosis in breast cancer.

Oncol Lett. 2020-9

[5]
Cell adhesion is regulated by CDK1 during the cell cycle.

J Cell Biol. 2018-6-21

[6]
Silencing Formin-like 2 inhibits growth and metastasis of gastric cancer cells through suppressing internalization of integrins.

Cancer Cell Int. 2018-6-1

[7]
A Rac1-FMNL2 signaling module affects cell-cell contact formation independent of Cdc42 and membrane protrusions.

PLoS One. 2018-3-26

[8]
Myosin-Driven Intracellular Transport.

Cold Spring Harb Perspect Biol. 2018-3-1

[9]
Knockdown of angiopoietin-like 4 inhibits the development of human gastric cancer.

Oncol Rep. 2018-2-7

[10]
FMNL2 and -3 regulate Golgi architecture and anterograde transport downstream of Cdc42.

Sci Rep. 2017-8-29

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