Oral cancer is a major public health burden worldwide. The lack of
biomarkers for early diagnosis has increased the difficulty in managing this disease. Recent studies have reported that
neutrophil gelatinase-associated lipocalin (NGAL), a secreted
glycoprotein, is upregulated in various
tumors. In our study, we found that NGAL was significantly downregulated in primary malignant and metastatic tissues of
oral cancer in comparison to normal tissues. The downregulation of NGAL was strongly correlated with both degree of differentiation and stage (I⁻IV); it can also serve as a prognostic
biomarker for
oral cancer. Additionally, tobacco
carcinogens were found to be involved in the downregulation of NGAL. Mechanistic studies revealed that knockdown of NGAL increased
oral cancer cell proliferation, survival, and migration; it also induced resistance against
cisplatin. Silencing of NGAL activated
mammalian target of rapamycin (mTOR)signaling and reduced autophagy by the liver
kinase B1 (LKB1)-activated
protein kinase (AMPK)-p53-Redd1 signaling axis. Moreover, cyclin-D1, Bcl-2, and
matrix metalloproteinase-9 (MMP-9) were upregulated, and
caspase-9 was downregulated, suggesting that silencing of NGAL increases
oral cancer cell proliferation, survival, and migration. Thus, from our study, it is evident that downregulation of NGAL activates the mTOR pathway and helps in the progression of
oral cancer.