It has been reported that lung cancer development and progression are induced by genetic mutations and various external factors. Recently, lung cancer genetic data are being used to identify novel factors capable of regulating cancer development and progression, thereby providing a therapeutic strategy for the intervention of lung cancers.

Various extrinsic and intrinsic factors from the tumor microenvironment (TEM) influence lung cancer progression. Recent studies have shown that toll-like receptors (TLRs) are expressed in lung cancers, suggesting that TLRs may be implicated in lung cancer progression. Although several studies have shown that stratifin (SFN, 14-3-3 sigma) facilitates lung cancer development and progression, the molecular and cellular mechanisms by which SFN is functionally involved in lung cancer progression, and the role of SFN in lung cancer progression in response to extrinsic stimulation, such as TLR agonist, are largely unknown.

In this study, we show that SFN expression remarkably up-regulates in lung cancer tissues through the analyses of The Cancer Genome Atlas (TCGA) data and primary non-small cell lung cancers (n = 31 of our cohort patients). Moreover, SFN positively regulates lung cancer progression through autophagy induction by facilitating the TRAF6-Vps34-BECN1 complex in response to an extrinsic TLR4 agonist (Figure 1). Together, our clinically comparative results and functional investigations of SFN expression in lung cancer will potentially contribute to translational approaches for the development of lung cancer therapeutic agents.

This study was carried out in collaboration with Dr. Eunyoung Chun's team in the R&D center at CHA Vaccine. Ji-Young Kim, a Ph.D. student at SKKU College of Medicine, contributed to this study as the first author.

Article: Kim, J. Y., Kim, M. J., Lee, J. S., Son, J., Kim, D. H., Lee, J. S., Jeong, S. K., Chun, E., & Lee, K. Y. (2022). Stratifin (SFN) regulates lung cancer progression via nucleating the Vps34-BECN1-TRAF6 complex for autophagy induction. Clinical and translational medicine (IF: 11.492), 12(6), e896. https://doi.org/10.1002/ctm2.896.