Biological Function And Molecular Mechanism Of Kif18A Influencing Proliferation, Migration And Anoikis In Human Breast Cancer Cell

Breast cancer is one of the most common tumor in women and is a leading cause of cancer-related deaths worldwide. Kinesins play important roles in the cell cycle. Previous study showed that Kinesins correlated with tumor development and progression. However, direct evidence for a role of Kif18A in tumorigenesis is currently lacking.Expression of Kifl8A was examined in 15 primary breast cancers and matched adjacent tissues by Western blot. Kif18A presented protein overexpression in over 60% of tumors. The result indicates that Kif18A may be involved in tumorigenesis.Functional analysis by RNAi revealed that downregulation of Kif18A decreased breast cancer cell capabilities in cell cycle progression, proliferation, migration, colony formation in soft agar and anoikis resistance. Furthermore, SPARC was downregulated and E-Cadherin was upregulated. Overexpression of Kif18A resulted in multinucleation.To explore the molecular mechanism by which downregulation of Kif 18A promoted anoikis, we examined the potential effect of Kif18A on the activation of several known pathway associated with anoikis. Only phosphorylated Akt was down-regulated in Kif18A RNAi cells. No difference in Erk activation or EGFR expression was observed after Kifl8A was suppressed, suggesting that PI3K-Akt, not MEK-Erk or EGFR signaling, might contribute to Kif18A-related survival in detached breast cancer cells.In vivo assay showed that inhibition of Kif18A expression also decreased tumor growth; overexpression of Kif18A promoted tumor growth.In summary, these data provide direct evidence that Kif18A influenced proliferation, migration in breast cancer cells. Suppression of Kif18A might promote anoikis through PI3K-Akt signal pathway. These data imply that Kif18A plays an important role in tumorigenesis of breast cancer. Kif18A may be an important cancer related gene.