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.
All together our results show that STK11ex1-2 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through STK11 inhibition might offer new opportunities.
Loss of LKB1 promotes cancer progression and influences therapeutic responses in preclinical studies; however, specific targeted therapies for lung cancer with LKB1 inactivation are currently unavailable.
We optimized and validated an IHC assay for LKB1 (clone Ley37D/G6) using a panel of lung cancer cell lines and tumors with known LKB1 mutations, including 2 patients with Peutz-Jeghers syndrome (PJS) who developed lung adenocarcinoma.
LKB1 status influences the molecular circuitry (Wnt/β-catenin pathway), cellular biology, and may serve as a potential therapeutic node in genetically defined subsets of lung cancer.
Loss of LKB1 is associated with consistent gene expression changes in resected human lung cancers and cell lines that differ substantially from the mouse model.
Overexpression of the LKB1 protein in human lung cancer is significantly associated with a decrease in activity and expression of the transcription factor SP1.
However, most of recent studies in LKB1 gene status only focus on point mutations and small deletion, and thus may underestimate the actual frequency of LKB1 genetic alteration in lung cancer.
Major signalling pathways that could play significant role in lung cancer therapy include (1) Growth promoting pathways (Epidermal Growth Factor Receptor/Ras/ PhosphatidylInositol 3-Kinase) (2) Growth inhibitory pathways (p53/Rb/P14ARF, STK11) (3) Apoptotic pathways (Bcl-2/Bax/Fas/FasL).
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.
Thus, LKB1-mutant lung cancers have deficits in nucleotide metabolism that confer hypersensitivity to DTYMK inhibition, suggesting that DTYMK is a potential therapeutic target in this aggressive subset of tumors.
In vivo, TUSC2 systemic delivery, by nanoparticle gene transfer, combined with MK2206 treatment markedly inhibited growth of tumors in a human LKB1-defective H322 lung cancer xenograft mouse model.
Collectively, our results decipher the mechanism through which LKB1 deficiency promotes lung cancer progression and metastasis, and provide a mechanistic rationale for therapeutic attack of these processes.
This study suggests that the combination of LKB1 gene therapy with low-dose cisplatin-based chemotherapy may be a potent therapeutic strategy for 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.
The discovery of cell proliferation and migration-related genes regulated by LKB1 is critical for unraveling molecular mechanisms of LKB1's role in the development and metastasis of lung cancer.