Abstract 384P
Background
Non-small cell lung cancer (NSCLC) makes up 85% of lung cancer cases, often with epidermal growth factor receptor (EGFR) mutations, targeted by tyrosine kinase inhibitors (TKIs) like Erlotinib and Osimertinib. Resistance arises from mutations, pathway alterations, and epithelial-mesenchymal transition (EMT). Lysocardiolipin acyltransferase (LYCAT), a mitochondrial enzyme in cardiolipin remodeling, promotes NSCLC proliferation, migration, and EMT, but its role in TKI resistance remains unclear.
Methods
LYCAT expression was evaluated in drug-resistant (ER/OR) and parental H358, H2170, and PC9 NSCLC cell lines using Western blotting, qRT-PCR, and immunofluorescence. siRNA-mediated LYCAT knockdown in H358ER cells assessed its role in resistance. Immunohistochemistry correlated LYCAT expression with NSCLC stages and smoking status.
Results
LYCAT protein was upregulated 3.8-fold in H358ER and 7.6-fold in PC9ER cells (p < 0.05). qPCR showed a 4.2-fold increase in these cells (p < 0.01). Immunofluorescence revealed increased nuclear/cytoplasmic LYCAT in H358ER (1.6-fold) and PC9ER (1.5-fold). Late-stage tumors showed higher LYCAT expression (75%) than early-stage (45%; p < 0.01), with smokers having elevated expression (68% vs. 34%; p < 0.001).
Conclusions
LYCAT mediates EGFR-TKI resistance, NSCLC progression, and smoking-related lung cancer through EMT and tumorigenicity regulation. Targeting LYCAT may offer therapeutic solutions for TKI resistance and improve patient outcomes.
Funding
Has not received any funding
Disclosure
All authors have declared no conflicts of interest.