Suppression of Kpnβ1 expression inhibits human breast cancer cell proliferation by abrogating nuclear transport of Her2

Breast cancer (BC) is one of the most fatal diseases and poses critical health problems worldwide. However, its mechanisms remain unclear. Consequently, there is an urgency to investigate the mechanisms involved in BC initiation and progression and identify novel therapeutics for its prevention and treatment. In this study, we identified karyopherin beta-1 (Kpn beta 1) as a possible novel therapeutic target for BC. Western blotting was used to evaluate the expression of Kpn beta 1 in four pairs of tumorous and adjacent non-tumorous tissues. The results revealed that the protein level of Kpn beta 1 was higher in the cancer samples compared with those in the corresponding normal samples. Immunohistochemistry was performed on 140 BC cases and indicated that Kpn beta 1 was significantly associated with clinical pathological variables. Kaplan-Meier curve revealed that high expression of Kpn beta 1 was related to poor BC patient prognosis. A starvation and re-feeding assay was used to imitate the cell cycle using the SKBR-3 cell line, indicating that Kpn beta 1 plays a critical role in cell proliferation. The Cell Counting Kit-8 assay revealed that SKBR-3 cells treated with Kpn beta 1-siRNA (siKpn beta 1) grew more slowly than the control cells, while flow cytometry revealed that low-Kpn beta 1 expressing SKBR-3 cells exhibited increased BC cell apoptosis. Furthermore, the interaction between Kpn beta 1 and Her2 was clearly observed by immunoprecipitation, indicating that Kpn beta 1-knockdown abrogated nuclear transport of Her2. In summary, our findings revealed that Kpn beta 1 is involved in the progression of BC and may be a useful therapeutic target.