CENPU promotes tumorigenesis and stem cell properties in triple‑negative breast cancer by suppressing lysosomal furin degradation.

Abstract

Centromere protein U (CENPU), a critical component of the kinetochore complex, structurally integrates with spindle microtubules to mediate chromosome segregation during mitosis. However, the association between CENPU expression levels and tumors is largely unknown. Immunohistochemistry and western blotting were used to analyze CENPU expression and prognostic value in breast cancer tissues. CENPU overexpressing/knockdown cell lines were constructed for 4D‑data‑independent acquisition quantitative proteomics and enrichment analyses. Functional assays, including flow cytometry, mammosphere formation, wound healing and Transwell assay, were used to assess the effects of CENPU on breast cancer stemness, migration and invasion. The associations among CENPU, nerve growth factor (NGF), proNGF and furin were also explored through western blotting, co‑immunoprecipitation and ELISA experiments. Finally, xenograft mouse models were established to verify the in vivo effects of CENPU on tumorigenesis and the inhibitory effect of furin inhibitor on CENPU‑promoted tumor growth. In the present study, immunohistochemistry and western blotting assessment of human breast cancer tissue specimens revealed a positive association between CENPU expression and the degree of invasiveness. The aforementioned functional analyses demonstrated that CENPU promoted stem cell‑like behavior and tumorigenicity, and induced malignancy in BC cells. Mechanistically, western blotting analysis demonstrated that CENPU promoted furin activity by inhibiting its lysosomal degradation. Furin, which is a precursor‑processing enzyme of (NGF), promoted the conversion of NGF precursor to NGF, which could promote BC stem cell properties in triple‑negative BC (TNBC). A tumorigenesis assay conducted in xenograft mouse models showed that CENPU promoted tumorigenesis, and treatment with a furin inhibitor suppressed this effect. The findings of the present study revealed that CENPU serves a critical role in furin‑mediated signaling responsible for tumorigenesis. Therefore, CENPU may be a novel molecular target in TNBC.