The Nanos3<sup>LSL</sup> mice were crossed with a non-small cell lung cancer (NSCLC) mouse model based on conditional expression of oncogenic KRas and homozygous loss of p53.
Whether the alterations of WDR79 protein expression are associated with TP53 mutation and clinicopathological and prognostic implications in the patients with surgically resected NSCLC have not been reported.
Thus, acquisition of TP53 mutations at progression is associated with more aggressive disease, shorter TKI responses and inferior OS in ALK+ NSCLC, comparable to primary TP53 mutated cases.
Expression of CTSL was markedly increased in human NSCLC tissues with mutant p53 (mut-p53), and p53 mutation positively correlated with metastasis of NSCLC patients.
<b>Conclusion:</b> HEATR1 inhibition activated p53 by reducing ribosome biogenesis, which subsequently led to NSCLC cell apoptosis and reduced cell survival through the p53-PUMA-BAX/BCL2 axis.
Introduction of exogenous wild‑type p53 mediates the regulation of oncoprotein 18/stathmin signaling via nuclear factor‑κB in non‑small cell lung cancer NCI‑H1299 cells.
In this study, we investigated the therapeutic effect of volasertib monotherapy (i.e., cytotoxicity, cell cycle distribution, apoptotic cell death, cellular senescence, and migration) in a panel of NSCLC cell lines differing in p53 status under both normal and reduced oxygen tension (<0.1% O<sub>2</sub> ).
This analysis showed histopathology-selective activation of PI3K/AKT and MAPK signalling in Kras mutant murine tumours, as well as high p38MAPK stress signalling in p53 null murine NSCLC.
NSCLC cell lines mutated for p53 and/or a component of the RAS/MAPK pathway and primary lung cancer-derived cells from Kras/Trp53 null mice were used as a preclinical model.
EI24 was significantly upregulated in mutated TP53NSCLC samples and significantly downregulated with the increase in the TP53 expression level in NSCLC.
Furthermore, SDH5 depletion inhibits p53 degradation via the ubiquitin/proteasome pathway, which promotes apoptosis and enhances radiosensitivity in NSCLC.
LCNEC can be subdivided in two main subtypes: the first harboring TP53/RB1 mutations (small cell lung carcinoma (SCLC)-like), the second with mutations in TP53 and STK11/KEAP1 (non-small cell lung carcinoma (NSCLC)-like).
Both in training set and validation set, the concentrations of SOX2, GAGE 7, MAGE A1, and P53 in NSCLC group increased prominently when compared to the healthy group (<i>P</i><0.05).
Our findings assign functional p53 as a determining factor for the observed radiosensitizing effect of volasertib in combination with radiotherapy for the treatment of NSCLC.
Collectively, our findings highlight a TP53/<i>miR-29s</i>/SETDB1 regulatory circuitry and assign a role of H3K9 methylation regulator to <i>miR-29s</i>, which may be a potential therapeutic target in the treatment of NSCLC.