Lung cancer is the leading cause of
cancer-related death across the globe. Despite the marked advances in detection and therapeutic approaches, management of
lung cancer patients remains a major challenge to oncologists which can be mainly attributed to late stage diagnosis,
tumor recurrence and chemoresistance. Therefore, to overthrow these limitations, there arises a vital need to develop effective
biomarkers for the successful management of this aggressive
cancer type. Notably,
TNF-alpha induced
protein 8 (TIPE), a
nuclear factor-kappa B (NF-κB)-inducible, oncogenic molecule and cytoplasmic
protein which is involved in the regulation of T lymphocyte-mediated immunity and different processes in
tumor cells such as proliferation, cell death and evasion of growth suppressors, might serve as one such
biomarker which would facilitate effective management of
lung cancer. Expression studies revealed this
protein to be significantly upregulated in different
lung cancer types, pathological conditions, stages and grades of lung
tumor compared to normal human lung tissues. In addition, knockout of TIPE led to the reduced proliferation, survival, invasion and migration of
lung cancer cells. Furthermore, TIPE was found to function through modulation of Akt/mTOR/STAT-3 signaling cascade. This is the first report which shows the involvement of TIPE in tobacco induced lung
carcinogenesis. It positively regulated
nicotine, NNK, NNN, and BaP induced proliferation, survival and migration of
lung cancer cells possibly via Akt/STAT-3 signaling. Thus, this
protein possesses important role in the pathogenesis of lung
tumor and hence it can be targeted for developing newer therapeutic interventions for the clinico-management of
lung cancer.