Krueppel-like factor 5–Erb-B2 receptor tyrosine kinase 2 oncogenic axis (KLF5–ERBB2 axis)

The KLF5–ERBB2 oncogenic axis is a critical regulatory circuit in which the transcription factor Krueppel-like factor 5 (KLF5) directly enhances the expression of the Erb-B2 receptor tyrosine kinase 2 (ERBB2/HER2) (PubMed: 26823719). This interaction is particularly prominent in gastric and breast cancers, where KLF5 binds to the ERBB2 promoter to drive high levels of HER2 protein, subsequently activating downstream PI3K/AKT and MAPK signaling pathways (PubMed: 29330278). The activation of this axis promotes tumor cell proliferation, survival, and invasion, often serving as a marker for poor prognosis. While current clinical interventions focus on inhibiting the ERBB2 component using monoclonal antibodies like Trastuzumab or small-molecule inhibitors like Lapatinib, the KLF5 component represents a significant node for potential combination therapy (PubMed: 31515465). Targeting KLF5 may help overcome resistance to HER2-targeted agents by reducing the transcriptional output of the ERBB2 gene and other compensatory survival signals.

Other names

KLF5-HER2 axisKLF5-ERBB2 signaling pathwayBTEB2-HER2 axisKLF5-NEU axis

The axis is targeted through the inhibition of the ERBB2 receptor tyrosine kinase activity or its extracellular dimerization, and experimentally through the suppression of KLF5-mediated transcriptional upregulation of the ERBB2 gene (PubMed: 26823719).