Liver kinase B1 (LKB1), as a serine/threonine kinase and tumor suppressor, is frequently mutated and inactivated in non-small cell lung cancer (NSCLC).
LKB1 is the third most frequently mutated gene in non-small cell lung cancer and serves as a master regulator of cell metabolism and polarity across a variety of model organisms.
LKB1 protein expression and Smad1 phosphorylation analysis in a cohort of non-small cell lung cancer patients demonstrated a negative correlation predominantly in a subset enriched in adenocarcinomas.
LKB1 is a commonly mutated tumor suppressor in non-small cell lung cancer that exerts complex effects on signal transduction and transcriptional regulation.
An expression quantitative trait locus variant for LKB1 gene predicts the clinical outcomes of chemotherapy in patients with non-small cell lung cancer.
As ID1 expression is up-regulated and confers poor prognosis in LKB1-deficient NSCLC, our results suggest that small molecules that inhibit CRTC2 and ID1 activity may provide therapeutic benefit to individuals with NSCLC.
Collectively, our study demonstrates that LINC00473 expression potentially serves as a robust biomarker for tumor LKB1 functional status that can be integrated into clinical trials for patient selection and treatment evaluation, and implicates LINC00473 as a therapeutic target for LKB1-inactivated NSCLC.
Data from several independent groups have provided information about the profiles of lung tumors with LKB1 inactivation and it is generally agreed that this alteration strongly predominates in non-small cell lung cancer, in particular adenocarcinomas, in smokers.
Hence, our findings support that enhanced E-cadherin by GA cooperates LKB1, leading to up-regulation of p-AMPK, and thus blocking of mTOR signaling pathway, which provide theoretical foundation for utilization of GA as a potential targeted drug against NSCLC harboring wild-type LKB1.