Nup93 regulates breast tumor growth by modulating cell proliferation and actin cytoskeleton remodeling. Life Sci Alliance 2020 Jan;3(1)
Date
01/22/2020Pubmed ID
31959624Pubmed Central ID
PMC6971368DOI
10.26508/lsa.201900623Scopus ID
2-s2.0-85078632811 (requires institutional sign-in at Scopus site) 31 CitationsAbstract
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 MWAuthor
Nikki K. Lytle PhD Assistant Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Actin CytoskeletonCarcinogenesis
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