Taken together, these observations suggest that fibronectin-induced stimulation of NSCLC cell proliferation requires activation of the Akt/mTOR/p70S6K pathway and is associated with inhibition of LKB1/AMPK signaling.
PIAs activated AMPK in LKB1-mutant non-small cell lung cancer (NSCLC) cell lines with similar concentration dependence as that required to inhibit Akt.
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.
We therefore studied TF gene (F3) expression and the status of genes coding for tumor protein p53 (TP53), phosphatase and tensin homolog (PTEN), and serine/threonine kinase 11 (STK11) in non-small cell lung cancer (NSCLC).
The STK11/LKB1 gene encodes a ubiquitously expressed serine/threonine kinase that is mutated in multiple sporadic cancers including non-small cell lung carcinomas, pancreatic cancers, and melanomas.
Liver kinase B1 (LKB1), as a serine/threonine kinase and tumor suppressor, is frequently mutated and inactivated in non-small cell lung cancer (NSCLC).
Our study attempted to establish LKB1 stable knockdown NSCLC cell line, detect alterations in gene expression and identify the genes regulated by LKB1.
Unlike most cancers of sporadic origin, in non-small cell lung cancer (NSCLC) nearly half of the tumors harbor somatic and homozygous inactivating mutations in LKB1.
Our data now suggest that, in contrast to MIF and d-DTs AMPK-activating properties in nontransformed cells, MIF and d-DT act cooperatively to inhibit steady-state phosphorylation and activation of AMPK in LKB1 wild type and LKB1 mutant human NSCLC cell lines.
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.
Multivariate analysis indicated that adenocarcinoma (P<0.05), lymph node metastasis (P<0.05), advanced TNM stage (P<0.001) and reduced expression of LKB1 (P<0.05) and Beclin1 (P<0.001) are all independent prognostic indicators for the survival of NSCLC patients.
In this study, we systematically analyzed how LKB1 and KRAS alteration, measured by mutation, gene expression (GE) and copy number (CN), are associated with brain metastasis in NSCLC.