Genetic and epigenetic alterations of the LKB1 gene and their associations with mutations in TP53 and EGFR pathway genes in Korean non-small cell lung cancers.
Our study provides insight into the molecular mechanism by which GDH1-mediated metabolic reprogramming of glutaminolysis mediates lung cancer metastasis and offers a therapeutic strategy for patients with LKB1-deficient lung cancer.
Inactivated mutations of LKB1, observed in 20-30% of nonsmall cell lung cancers (NSCLC), contribute significantly to lung cancer malignancy progression.
As LKB1 is a target for mutational inactivation in lung cancer and was recently shown to regulate hepatic Crtc2/CREB transcriptional activity in mice, we now present evidence suggesting disruption of an LKB1/Crtc pathway in cancer.
Expression profiling in human lung cancer cell lines and mouse lung tumours identified a variety of metastasis-promoting genes, such as NEDD9, VEGFC and CD24, as targets of LKB1 repression in lung cancer.
The aim of this review is to discuss interactions of LKB1 with the tumor microenvironment and the potential applications of this knowledge in predicting response to treatment in lung cancer.
The present review considers the frequency and pattern of LKB1 mutations in lung cancer and the distinct biological pathways in which the LKB1 protein is involved in the development of this type of cancer.
Further, CP alone or in combination with rapamycin strongly inhibited the in vitro and in vivo growth of tumors harboring mutations in KEAP1 or both KEAP1 and LKB1 that are frequently observed in lung cancer.
Moreover, mutations and misregulation of LKB1 have been reported to occur in most types of tumors and are among the most common aberrations in lung cancer.
These pathways are clinically prognostic and predictive, including the TP53-AXIN-ARHGEF17 combination in liver and CYLC2-STK11-STK11IP in lung cancer, which we validate in independent cohorts.
Our study also provides new evidence to support the critical role of liver kinase B1 in the pathogenesis of human papillomavirus-related lung cancer and suggests novel therapeutic targets.
In this paper, E6, LKB1, SP1, and hTERT mRNA expression levels were detected in brushing cells of patients with lung cancer (n = 106) and with benign lung disease (n = 68) by qRT-PCR.
Mechanistically, we uncovered that autophagy was induced upon loss of <i>circHIPK3</i> via the <i>MIR124-3p</i>-STAT3-PRKAA/AMPKa axis in STK11 mutant lung cancer cell lines (A549 and H838).
Our findings provide evidence of how LKB1 loss of function promotes lung cancer malignancy through remodeling of extracellular matrix microenvironment, and identify LOX as a potential target for disease treatment in lung cancer patients.
Overexpression of the LKB1 protein in human lung cancer is significantly associated with a decrease in activity and expression of the transcription factor SP1.