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Life Sci Alliance. 2020 Jan 20;3(1). pii: e201900623. doi: 10.26508/lsa.201900623. Print 2020 Jan.

Nup93 regulates breast tumor growth by modulating cell proliferation and actin cytoskeleton remodeling.

Author information

1
Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
2
Paul F. Glenn Center for Biology of Aging Research at The Salk Institute, La Jolla, CA, USA.
3
Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.
4
The Razavi Newman Integrative Genomics and Bioinformatics Core (IGC), The Salk Institute for Biological Studies, La Jolla, CA, USA.
5
Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA hetzer@salk.edu.

Abstract

Nucleoporin 93 (Nup93) expression inversely correlates with the survival of triple-negative breast cancer patients. However, our knowledge of Nup93 function in breast cancer besides its role as structural component of the nuclear pore complex is not understood. Combination of functional assays and genetic analyses suggested that chromatin interaction of Nup93 partially modulates the expression of genes associated with actin cytoskeleton remodeling and epithelial to mesenchymal transition, resulting in impaired invasion of triple-negative, claudin-low breast cancer cells. Nup93 depletion induced stress fiber formation associated with reduced cell migration/proliferation and impaired expression of mesenchymal-like genes. Silencing LIMCH1, a gene responsible for actin cytoskeleton remodeling and up-regulated upon Nup93 depletion, partially restored the invasive phenotype of cancer cells. Loss of Nup93 led to significant defects in tumor establishment/propagation in vivo, whereas patient samples revealed that high Nup93 and low LIMCH1 expression correlate with late tumor stage. Our approach identified Nup93 as contributor of triple-negative, claudin-low breast cancer cell invasion and paves the way to study the role of nuclear envelope proteins during breast cancer tumorigenesis.

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