Roles of ARF tumour suppressor protein in lung cancer: time to hit the nail on the head!

Abstract

Owing to its poor prognosis, the World Health Organization (WHO) lists lung cancer on top of the list when it comes to growing mortality rates and incidence. Usually, there are two types of lung cancer, small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC), which also includes adenocarcinoma, squamous cell carcinoma and large cell carcinomas. ARF, also known in humans as p14ARF and in the mouse as p19ARF, is a nucleolar protein and a member of INK4, a family of cyclin-independent kinase inhibitors (CKI). These genes are clustered on chromosome number 9p21 within the locus of CDKN2A. NSCLC has reported the role of p14ARF as a potential target. p14ARF has a basic mechanism to inhibit mouse double minute 2 protein that exhibits inhibitory action on p53, a phosphoprotein tumour suppressor, thus playing a role in various tumour-related activities such as growth inhibition, DNA damage, autophagy, apoptosis, cell cycle arrest and others. Extensive cancer research is ongoing and updated reports regarding the role of ARF in lung cancer are available. This article summarizes the available lung cancer ARF data, its molecular mechanisms and its associated signalling pathways. Attempts have been made to show how p14ARF functions in different types of lung cancer providing a thought to look upon ARF as a new target for treating the debilitating condition of lung cancer.