RT Journal Article
SR Electronic
T1 Nup93 regulates breast tumor growth by modulating cell proliferation and actin cytoskeleton remodeling
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900623
DO 10.26508/lsa.201900623
VO 3
IS 1
A1 Simone Bersini
A1 Nikki K Lytle
A1 Roberta Schulte
A1 Ling Huang
A1 Geoffrey M Wahl
A1 Martin W Hetzer
YR 2020
UL https://www.life-science-alliance.org/content/3/1/e201900623.abstract
AB 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.