BUB1 mitotic checkpoint serine/threonine kinase B (BUB1b) has been unequivocally identified as an oncogene in various cancers. However, the potential mechanism by which BUB1b orchestrates the progression of lung adenocarcinoma (LUAD) remains unclear. Here we found that both the transcript and protein levels of BUB1b were dramatically upregulated in tumor tissues and contributed to the dismal prognosis of LUAD patients. Moreover, gain- and loss-of-function assays, conducted both in vitro and in vivo, confirmed that BUB1b enhanced the viability of LUAD cells. Mechanistically, BUB1b forms a complex with OTUD3 and NRF2 and stabilizes the downstream NRF2 signaling pathway to facilitate insensitivity to ferroptosis and chemotherapy. In BALB/c nude mice bearing subcutaneous tumors that overexpress BUB1b, a combined strategy of ML385 targeting and chemotherapy achieved synergistic effects, inhibiting tumor growth and obviously improving survival. Taken together our study uncovered the underlying mechanism by which BUB1b promotes the progression of LUAD and proposed a novel strategy to enhance the efficacy of chemotherapy.
Keyphrases
- signaling pathway
- locally advanced
- end stage renal disease
- induced apoptosis
- oxidative stress
- cell death
- chronic kidney disease
- gene expression
- cell cycle
- protein kinase
- newly diagnosed
- dna damage
- epithelial mesenchymal transition
- chemotherapy induced
- metabolic syndrome
- peritoneal dialysis
- radiation therapy
- risk assessment
- tyrosine kinase
- young adults
- insulin resistance
- skeletal muscle
- patient reported outcomes
- amino acid
- endoplasmic reticulum stress