ΔNp63α promotes radioresistance in esophageal squamous cell carcinoma through the PLEC-KEAP1-NRF2 feedback loop.

ABSTRACT: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers and is highly prevalent in China, exhibiting resistance to current treatments. ΔNP63α, the main isoform of p63, is frequently amplified in ESCC and contributes to therapeutic resistance, although the molecular mechanisms remain unknown. Here, we report that ΔNP63α is highly expressed in ESCC and is associated with radioresistance by reducing ROS level. Furthermore, ΔNP63α plays a critical role in radioresistance by directly transactivating the expression of PLEC. PLEC competitively interacts with KEAP1, resulting in the release of NRF2 from KEAP1 and its translocation from the cytosol to the nucleus, where it activates gene expression to facilitate ROS elimination. Additionally, radiotherapy-induced ROS also ac

SUBMITTER: Tao J 

PROVIDER: S-EPMC11538512 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature