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Nup93 regulates breast tumor growth by modulating cell proliferation and actin cytoskeleton remodeling. Life Sci Alliance 2020 Jan;3(1)

Date

01/22/2020

Pubmed ID

31959624

Pubmed Central ID

PMC6971368

DOI

10.26508/lsa.201900623

Scopus ID

2-s2.0-85078632811 (requires institutional sign-in at Scopus site)   31 Citations

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.

Author List

Bersini S, Lytle NK, Schulte R, Huang L, Wahl GM, Hetzer MW

Author

Nikki K. Lytle PhD Assistant Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Actin Cytoskeleton
Carcinogenesis
Cell Line
Cell Line, Tumor
Cell Proliferation
Chromatin
Epithelial-Mesenchymal Transition
Female
Gene Expression Regulation, Neoplastic
Humans
LIM Domain Proteins
Nuclear Pore
Nuclear Pore Complex Proteins
RNA Interference
Triple Negative Breast Neoplasms