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Keratin type I cytoskeletal 14 (KRT14) is a type I intermediate filament protein that serves as a fundamental structural component of the basal layer of stratified squamous epithelia. It forms obligate heterodimers with Keratin 5 (KRT5), creating a dense cytoskeletal network that provides mechanical integrity and protects keratinocytes from physical trauma. Beyond its structural function, KRT14 plays a critical role in regulating cellular processes such as proliferation, migration, and differentiation by modulating signaling pathways like PI3K/Akt and Notch1. Mutations in the KRT14 gene are primarily associated with Epidermolysis Bullosa Simplex (EBS), a group of genetic disorders characterized by skin fragility and blistering due to the collapse of the keratin network. In the context of oncology, KRT14 is often overexpressed in invasive cancer cells and cancer stem cells, where it is linked to increased metastatic potential and resistance to chemotherapy. Current therapeutic research focuses on gene-editing technologies, such as AAV-mediated gene targeting and CRISPR/Cas9, to correct or disrupt mutant alleles in EBS patients. Additionally, RNA interference strategies are being explored to silence KRT14 expression in various cancers to inhibit tumor invasion and progression.
Gene targeting and RNA interference to disrupt mutant allele expression or reduce protein levels in cancer cells.
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