KIF20A promotes triple-negative breast cancer progression via activation of the IL-17 signaling pathway

Abstract

Background

Triple-negative breast cancer (TNBC), the only breast cancer subtype lacking effective targeted therapies, is associated with a poor prognosis. Emerging evidence highlights the oncogenic role of kinesin family member 20A (KIF20A) in human malignancies, though its mechanistic contributions to TNBC progression remain poorly understood.

Methods

Candidate target genes were screened via bioinformatic analysis. Following KIF20A knockdown, we utilized cell counting kit-8, 5-Ethynyl-2′-deoxyuridine staining, transwell, and wound healing assays to assess TNBC cell viability, proliferative capacity, migratory ability, and invasive potential of TNBC cells. In vivo, we measured the volume, weight, and proliferation of solid tumors. Moreover, the downstream pathway of KIF20A was screened by bioinformatic analysis and validated by an agonist and an inhibitor for the interleukin 17 (IL-17) pathway. The expression levels of proteins associated with the IL-17 pathway were assessed via Western blot.

Results

KIF20A, highly overexpressed in TNBC, was screened out as a promising target gene. In vitro, KIF20A knockdown significantly impaired TNBC cell viability, proliferation, migration, and invasion. In vivo, KIF20A knockdown suppressed the growth and proliferation of solid tumors in nude mice xenograft models. Mechanistically, the IL-17 signaling pathway was screened out and the expression of proteins in this pathway was suppressed by KIF20A knockdown. The agonist for the IL-17 signaling countered the impact of KIF20A knockdown on TNBC progression. Direct inhibition of IL-17 showed a similar effect as KIF20A silencing on TNBC cells.

Conclusion

KIF20A downregulation suppresses TNBC progression via the inactivation of the IL-17 signaling pathway, suggesting KIF20A as a potential therapeutic target for TNBC.