KLF13 promotes breast cancer progression through the HTRA1 and the Hedgehog signaling pathway.

Background: Kruppel-like factor 13 (KLF13) influences both immune system disorders and cancer progression, whereas the effects of KLF13 on the immune escape and breast cancer remain incompletely understood.

Research design and methods: KLF13 expression was assessed in breast cancer tumor tissues. The roles of KLF13 in cell proliferation, migration, and immune evasion were assessed. RNA sequencing was used to identify the differentially expressed genes and signaling. Chip-seq and luciferase assays were performed to validate binding of KLF13 to its downstream genes. In vivo studies were conducted to confirm the function of KLF13. The mechanisms were elucidated using recovery assays.

Results: KLF13 levels were higher in breast cancer tissue. Silencing KLF13 markedly diminished cell proliferation, migration, mammosphere formation, and immune evasion by suppressing the levels of HTRA1 and the Hedgehog signaling pathway. KLF13 overexpression potentiated breast cancer aggressiveness and enhanced immune evasion. Inhibiting KLF13 delayed development of cancer xenografts, as well as curtailing tumor growth, which were reversed by co-expression of HTRA1. Clinical relevance results suggested a positive correlation between KLF13, HTRA1 and density of CD8T cells in human breast cancer patients.

Conclusions: KLF13 can serve as a tumor promoter in breast cancer by influencing HTRA1 and the Hedgehog signaling pathway.