Non-small cell lung cancer (NSCLC), with adenocarcinoma being the major histopathologic subtype, develops in distinct steps involving the progressive accumulation of genetic alterations. These include somatic oncogenic K-Ras and EGFR mutually exclusive mutations and inactivating mutations in the p53 tumour suppressor, leading to activation of IKKbeta/canonical (RelA/p65-p50) NF-kappaB signalling.
However, the mechanism(s) by which canonical NF-kappaB contributes to NSCLC development or progression is still under investigation. Further, the impact and mechanism of action of IKKbeta/noncanoncal (RelB-p52) NF-kappaB signalling on NSCLC remains elusive.
To better define the impact of IKKbeta/canonical versus IKKbeta/noncanoncal NF-kappaB signalling, we developed independent in vivo mouse and human lung cancer models and showed that while IKKbeta-RelA/p65 act as NSCLC tumour promoters, CHUK/IKKbeta but not p52 acts as a major NSCLC tumour suppressor.
Using high-throughput molecular analysis (RNA-seq, Nanostring miRNA) in conjunction with bioinformatics analysis, and several biochemical, cell and molecular biology assays, we defined mechanisms by which these two major NF-kappaB signalling pathways contribute to NSCLC development and progression.
Dr Evangelos Kolettas is Associate Professor of Molecular Cell Biology at the School of Medicine, University of Ioannina, Greece, and Faculty Member at the Institute of Molecular Biology and Biotechnology, FORTH.
Following his BSc (Hons) in Biochemistry at King’s College London, and PhD in the Genetics Division, MRC NIMR, he joined the Department of Biochemistry, Charing Cross and Westminster Medical School, University of London as a postdoctoral researcher. Currently, his research group focuses on molecular and cellular cancer biology and senescence using diverse models and approaches.