The Functional Study of RSK4 in Human Non-small cell lung cancer

Abstract

The p90 ribosomal protein S6 kinase 4 (RSK4) is a serine-threonine kinase that functions downstream of the mitogen-activated protein kinase (MAPK) signaling pathway and regulates cellular processes. RSK4 was confirmed to be highly expressed in non-small cell lung cancer (NSCLC) patients with EGFR mutations through the Gene Expression Omnibus (GEO) database. The protein expression of RSK4 was upregulated in cancer tissues compared with normal tissues in patients with lung cancer. In particular, it was highly expressed NSCLC cell lines with EGFR mutations. Furthermore, when RSK4 was inhibited, apoptosis was induced only in EGFR mutation cell lines. Additionally, knockdown of RSK4 inhibited Akt phosphorylation and increased the mRNA expression of PUMA, a BH3-only protein. Interestingly, other BH3-only proteins showed no differences in expression at the mRNA and protein levels. Next, inhibition of RSK4 induced the nuclear translocation of p65, which regulates the transcription of PUMA. In summary, these findings demonstrated that the downregulation of RSK4 inhibits the survival of cells with EGFR mutations through the Akt/p65/PUMA signaling pathway. This suggests the potential of RSK4 as a novel therapeutic target for NSCLC with EGFR mutation. Keywords: RSK4, Non-small cell lung cancer, EGFR mutation, Apoptosis, Therapeutic target