Somatic nuclear auto-antigenic sperm protein sensitizes human breast cancer cells to 5-Fluorouracil.

Yanjing Huang, Shenghui Yang, Weiling Yu, Ling Gui

Cancer chemotherapy and pharmacology 2022 Apr

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To assess the potential role of nuclear auto-antigenic sperm protein (NASP) in the cellular sensitivity to 5-Fluorouracil (5-FU) in breast cancer cells. The expression of two NASP isotypes, namely somatic NASP (sNASP) and testis NASP (tNASP) in breast cancer lines were detected under 5-FU treatment using real-time polymerase chain reaction and western blot assays. NASP effect on cellular viability and apoptosis under 5-FU treatment were evaluated. The interaction between NASP and its downstream proteins were evaluated using the co-immunoprecipitation (Co-IP) assays. 5-FU significantly decreased the mRNA and protein expression levels of sNASP. Inhibition of sNASP increased cellular viability, colony formation ability, but reduced apoptosis in tested cell lines in response to 5-FU, which were reversed by sNASP over-expression. Further study reveals 5-FU disrupts sNASP/TNF receptor-associated factor 6 (TRAF6) complex, potentiates cellular sensitivity to 5-FU via NK-kB. Our findings suggest sNASP is a novel molecular target having potential to overcome the resistance to 5-FU in breast cancer cells. © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Citation

Yanjing Huang, Shenghui Yang, Weiling Yu, Ling Gui. Somatic nuclear auto-antigenic sperm protein sensitizes human breast cancer cells to 5-Fluorouracil. Cancer chemotherapy and pharmacology. 2022 Apr;89(4):559-564