Journal
MOLECULAR AND CELLULAR BIOCHEMISTRY
Volume 476, Issue 9, Pages 3303-3318Publisher
SPRINGER
DOI: 10.1007/s11010-021-04060-1
Keywords
Cancer; Lung; TIPE1; Biomarker; Tobacco; Akt; mTOR; STAT-3; Targeted therapy
Categories
Funding
- Department of Biotechnology (DBT), Government of India [BT/556/NE/UEXCEL/2016, BT/PR16998/NER/95/449/2015]
- UGC, New Delhi, India
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Lung cancer is a prevalent neoplasm globally, with factors such as tobacco smoking and exposure to carcinogens playing a significant role in its development. The protein TIPE1 shows promise as an important biomarker in lung cancer pathogenesis, with potential therapeutic implications.
Lung cancer represents one of the most prevalent neoplasms across the globe. Tobacco smoking, exposure to different occupational and environmental carcinogens, and various dietary factors are strongly implicated in the development of lung cancer. The 5-year survival rate of lung cancer is extremely poor which can be attributed to its propensity for early spread, lack of appropriate biomarkers and proper therapeutic strategies for this aggressive neoplasm. Emerging evidence suggests tumor necrosis factor-alpha-induced protein eight like 1 (TIPE1 or TNFAIP8L1), which functions as a cell death regulator, to hold high prospect as an important biomarker. Interestingly, this protein was found to be significantly downregulated in human lung cancer tissues compared to normal lung tissues. In addition, this protein exerted marked downregulation in different stages and grades of lung tumor. Further knockout of TIPE1 led to the enhancement in proliferation, survival, migration and invasion of NCIH460 human lung cancer cells through modulation of Akt/mTOR/STAT-3 signaling cascade. In addition, TIPE1 was found to be involved in nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, N-nitrosonornicotine and benzo[a]pyrene-mediated lung cancer through enhanced proliferation, survival and migration of lung cancer cells. Altogether, this newly identified protein plays a critical role in lung cancer pathogenesis and possess enormous prospect to serve as an important tool in the effective management of this aggressive neoplasm.
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