Targeting the up-regulated CNOT3 reverses therapeutic resistance and metastatic progression of EGFR-mutant non-small cell lung cancer.

ABSTRACT: Lung cancer is the leading cause of cancer-related mortality worldwide. CNOT3, a subunit of the CCR4-NOT complex, has recently been suggested to be overexpressed in lung cancer and involved in tumor malignancy. However, its precise role and the underlying mechanisms still need to be fully revealed. In the present study, we found in lung cancer cells the expression of CNOT3 could be regulated by EGFR signaling pathway and c-Jun, a transcription factor downstream of EGFR, transcriptionally regulated its expression. Interestingly, CNOT3 could inversely regulate the expression of c-Jun via modulating its translation. Thus, a feedback loop existed between c-Jun and CNOT3. CNOT3 reduction post EGFR blockade facilitated the drug-induced cell death, and simultaneously inhibited cell proliferation

SUBMITTER: Jing L 

PROVIDER: S-EPMC10622567 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature