KIF18B promotes breast cancer cell proliferation, migration and invasion by targeting TRIP13 and activating the Wnt/β-catenin signaling pathway.

Abstract

Kinesin superfamily member 18B (KIF18B) has previously been reported to be upregulated in breast cancer (BC) and is involved in BC tumorigenesis. Therefore, the present study aimed to investigate the effects and underlying mechanisms of KIF18B in BC. Comprehensive bioinformatics analysis was performed, using data from The Cancer Genome Atlas. KIF18B knockdown and thyroid hormone receptor-interacting protein 13 (TRIP13) overexpression in BC cells were induced via transfection, by using the short hairpin RNA-KIF18B and overexpression-TRIP13 vectors, respectively. Cellular processes, including proliferation, migration and invasion were assessed using colony formation, wound healing and Transwell assays, respectively. mRNA and protein expression levels were determined using reverse transcription-quantitative PCR and western blot analysis, respectively. Protein-protein interactions were determined using co-immunoprecipitation. The results demonstrated that the KIF18B expression levels were upregulated in BC, particularly in triple-negative BC (TNBC) tissues and cell lines. KIF18B knockdown inhibited the proliferation, migration and invasion of HCC-1937 TNBC cells. Furthermore, MMP12 and MMP9 protein expression levels were decreased by KIF18B knockdown. TRIP13 expression was also demonstrated to be upregulated in BC, particularly in TNBC tissues and cell lines. TRIP13 expression levels positively correlated with those of KIF18B in BC tissues and cells, and further analysis verified that TRIP13 and KIF14B were able to directly bind to each other. However, TRIP13 overexpression abolished the effects of KIF18B knockdown on HCC-1937 cells. Furthermore, KIF18B knockdown decreased β-catenin, c-Myc and cyclin D1 protein expression levels; however, TRIP13 overexpression resulted in the recovery of all respective protein expression levels. On the whole, the present study demonstrates that KIF18B promotes BC malignant events, including the proliferation, migration and invasion of TNBC cells. These results indicate that KIF18B may play an oncogenic role in BC by upregulating TRIP13 expression, thereby activating the Wnt/β-catenin signaling pathway.