Document Type
Article
Publication Date
12-13-2021
Publication Title
Nat Commun
Keywords
JGM
JAX Source
Nat Commun 2021 Dec 13; 12(1):7216
Volume
12
Issue
1
First Page
7216
Last Page
7216
ISSN
2041-1723
PMID
34903738
DOI
https://doi.org/10.1038/s41467-021-27451-w
Abstract
Mechanical signals from the extracellular microenvironment have been implicated in tumor and metastatic progression. Here, we identify nucleoporin NUP210 as a metastasis susceptibility gene for human estrogen receptor positive (ER+) breast cancer and a cellular mechanosensor. Nup210 depletion suppresses lung metastasis in mouse models of breast cancer. Mechanistically, NUP210 interacts with LINC complex protein SUN2 which connects the nucleus to the cytoskeleton. In addition, the NUP210/SUN2 complex interacts with chromatin via the short isoform of BRD4 and histone H3.1/H3.2 at the nuclear periphery. In Nup210 knockout cells, mechanosensitive genes accumulate H3K27me3 heterochromatin modification, mediated by the polycomb repressive complex 2 and differentially reposition within the nucleus. Transcriptional repression in Nup210 knockout cells results in defective mechanotransduction and focal adhesion necessary for their metastatic capacity. Our study provides an important role of nuclear pore protein in cellular mechanosensation and metastasis.
Recommended Citation
Amin R,
Shukla A,
Zhu J,
Kim S,
Wang P,
Tian S,
Tran A,
Paul D,
Cappell S,
Burkett S,
Liu H,
Lee M,
Kruhlak M,
Dwyer J,
Simpson R,
Hager G,
Ruan Y,
Hunter K.
Nuclear pore protein NUP210 depletion suppresses metastasis through heterochromatin-mediated disruption of tumor cell mechanical response. Nat Commun 2021 Dec 13; 12(1):7216
Comments
This article is licensed under a Creative Commons Attribution 4.0 International License.