The Role Of KIF1Bβ In The Development Of Heptocellular Carcinoma

The kinesin superfamily member involves in the transport of organelles and vesicles in amicrotubule-and ATP-dependent manner. Up to now, the kinesins have included14sub-families and45members. KIF1Bβ (kinesin family member1B, isoform b), one of themembers of the kinesins, maps to chromosome1p36.2. Loss of heterozygosity (LOH)involving1p36.2is a common genetic lesion in a broad ranges of human cancers, implyingthat this region might contain potential tumor suppressor(s). Indeed, KIF1Bβ has previouslybeen identified as a potential1p36.2tumor suppressor in neuroblastoma. Recently, by usinggenome-wide association study (GWAS), we identified1p36.22as a new susceptibility locusfor hepatocellular carcinoma (HCC) in chronic hepatitis B virus carriers, implying that theKIF1Bβ might be involved in the pathogenesis of this malignancy. In the present study, weexplored the role of KIF1Bβ in the development of HCC.We assessed the mRNA and protein expression of KIF1Bβ by quantitative RT-PCR andwestern blots analyses in normal liver cell lines and HCC cell lines. We detected greaterexpression of KIF1Bβ in normal liver cells than in HCC cell lines. Then, we examined theeffects of KIF1Bβ on cell migration, invasion, proliferation, cell cycle, apoptosis andautophagy by disturbing the expression of KIF1Bβ. We found that knocking-down ofKIF1Bβ promotes the cell invasion and metastasis in vitro. Whereas, the enhanced expressionof KIF1Bβ induces cell apoptosis and knocking-down of KIF1Bβ protects against apoptosis.The knocking-down of KIF1Bβ increases the rate of cells in S phase and decreases the cellsin G0-G1phase. We also assessed the role of KIF1Bβ in lysosomal redistribution andautophagy in HCC cells. We found that knocking-down of KIF1Bβ promotes lysosomeredistribution to cell nuclear periphery and autophagy, while overexpression of KIF1Bβinduces lysosomal cluster in cell periphery and suppresses autophagy.We further investigated and validated the interacting proteins of KIF1Bβ by IP/MS andCo-IP technology, respectively. We found that the KIF1Bβ can interact with Axin1, GSK3βand β-catenin, all of which are components of Wnt signaling pathway. Further,knocking-down of KIF1Bβ enhanced β-catenin accumulation and the downstream targets ofWnt (cyclin D1and MMP-9).Taken together, our data support a pivotal role for KIF1Bβ in the development of HCC.Aberrant Wnt signaling may be a hallmark of progression to this malignancy.