Lung cancer represents the most common cause of
cancer deaths in the world, constituting around 11.6% of all new
cancer cases and 18.4% of
cancer-related deaths. The propensity for early spread, lack of suitable
biomarkers for early diagnosis, as well as prognosis and ineffective existing
therapies, contribute to the poor survival rate of
lung cancer. Therefore, there is an urgent need to develop novel
biomarkers for early diagnosis and prognosis which in turn can facilitate newer therapeutic avenues for the management of this aggressive
neoplasm. TIPE2 (
tumor necrosis factor-α-induced
protein 8-like 2), a recently identified cytoplasmic
protein, possesses enormous potential in this regard. Immunohistochemical analysis showed that TIPE2 was significantly upregulated in different stages and grades of
lung cancer tissues compared to normal lung tissues, implying its involvement in the positive regulation of
lung cancer. Further, knockout of TIPE2 resulted in significantly reduced proliferation, survival, and migration of human
lung cancer cells through modulation of the Akt/mTOR/NF-κB signaling axis. In addition, knockout of TIPE2 also caused arrest in the S phase of the cell cycle of
lung cancer cells. As tobacco is the most predominant risk factor for
lung cancer, we therefore evaluated the effect of TIPE2 in tobacco-mediated lung
carcinogenesis as well. Our results showed that TIPE2 was involved in
nicotine-,
nicotine-derived
nitrosamine ketone (NNK)-,
N-nitrosonornicotine (NNN)-, and
benzo[a]pyrene (BaP)-mediated
lung cancer through inhibited proliferation, survival, and migration via modulation of
nuclear factor kappa B (NF-κB)- and NF-κB-regulated gene products, which are involved in the regulation of diverse processes in
lung cancer cells. Taken together, TIPE2 possesses an important role in the development and progression of
lung cancer, particularly in tobacco-promoted
lung cancer, and hence, specific targeting of it holds an enormous prospect in newer therapeutic interventions in
lung cancer. However, these findings need to be validated in the in vivo and clinical settings to fully establish the diagnostic and prognostic importance of TIPE2 against
lung cancer.