Significance of stratifin in early progression of lung adenocarcinoma and its potential therapeutic relevance

Lung cancer is the most common cause of global cancer-related mortality, and the main histological type is adenocarcinoma, accounting for 50% of non-small cell lung cancer. In 2015, the World Health Organization (WHO) histological classification defined the concepts of "adenocarcinoma in situ" (AIS) and "minimally invasive adenocarcinoma" (MIA), which are considered to be adenocarcinomas at a very early stage. Although AIS and MIA have a very favorable outcome, once they progress to early but invasive adenocarcinoma (eIA), they can sometimes have a fatal outcome. We previously compared the expression profiles of eIA and AIS, and identified stratifin (SFN; 14-3-3 sigma) as a protein showing significantly higher expression in eIA than in AIS. Expression of SFN is controlled epigenetically by DNA demethylation, and its overexpression is significantly correlated with poorer outcome. In vitro and in vivo analyses have shown that SFN facilitates early progression of adenocarcinoma by enhancing cell proliferation. This review summarizes genetic and epigenetic abnormalities that can occur in early-stage lung adenocarcinoma and introduces recent findings regarding the biological significance of SFN overexpression during the course of lung adenocarcinoma progression. Therapeutic strategies for targeting SFN are also discussed.