Control of EGFR-L858R oncogenic signaling pathway by the p14ARF tumor suppressor in lung adenocarcinoma.
type: Dataset
description: Control of EGFR-L858R oncogenic signaling pathway by the p14ARF tumor suppressor in lung adenocarcinoma. The EGF receptor (EGFR) is a strong oncogene involved in lung carcinogenesis. In these cancers, sensitivity to inhibitors of the EGFR tyrosine kinase activity (EGFR-TKI) has been shown to be related to the presence of activating mutations in the TK domain of EGFR (mainly L858R and Del19). However, the association between mutations and responsiveness to EGFR-TKI based treatment is more complex than previously envisioned, underlying the pressing need to study thoroughly the molecular mechanisms of lung cancer growth. We previously showed that almost all lung cancer with EGFR activated mutations has very low or undetectable levels of the p14ARF tumor suppressor protein. These results led us to postulate that expression of p14ARF is an efficient break against clonal proliferation of these cells. We report for the first time a relationship between p14ARF and mutant EGFR-L858R in which p14ARF inhibits the growth of EGFR-L858R expressing cells by inducing apoptosis. The p14ARF tumor suppressor effects involve an original STAT3 pro-apoptotic function that drives the inhibition of the anti-apoptotic Bcl-2 protein. Moreover, we show that the EGFR-L858R mutant maintains their survival and proliferation characteristics by inhibiting p14ARF expression and consequently the STAT3/Bcl-2 pro-apoptotic pathway. Our results also identify p14ARF as a new transcriptional target of STAT3, therefore providing evidence of a positive feed-back loop that could maintain STAT3 pro-apoptotic pathway. Based on these data, we suggest that manipulation of this pathway could be a therapeutic strategy for lung cancer treatment.
identifier: NNT: 2011GRENV084
issued: 2026-05-30T01:42:51.739053
language: fr
modified: 2026-05-30T01:42:51.739060
contact point: Organization
  fn: CCSD
keyword: apoptose
keyword: apoptosis
keyword: bcl--2
keyword: bcl-2
keyword: cancer-du-poumon
keyword: egfr-mute-l858r
keyword: infoeu-reposemanticsdoctoralthesis
keyword: lung-cancer
keyword: mutated-egfr-l858r
keyword: p14arf-proteine-suppresseur-de-tumeur
keyword: sdvsalife-sciences-q-bioagricultural-sciences
keyword: stat3
keyword: theses
keyword: tumor-suppressor-protein-p14arf
landing page: https://theses.hal.science/tel-00767340

Control of EGFR-L858R oncogenic signaling pathway by the p14ARF tumor suppressor in lung adenocarcinoma.
type: Distribution
format: HTML
issued: 2026-05-30T01:42:51.893904
modified: 2026-05-30T01:42:51.693955
access URL: https://theses.hal.science/tel-00767340

test_moissonnage_selune
type: Agent