Preprint Article Version 1 This version is not peer-reviewed

NGAL is Downregulated in Oral Squamous Cell Carcinoma and Leads to Increased Survival, Proliferation, Migration, and Chemoresistance

Version 1 : Received: 3 May 2018 / Approved: 3 May 2018 / Online: 3 May 2018 (12:47:14 CEST)

How to cite: Monisha, J.; Roy, N.K.; Padmavathi, G.; Banik, K.; Bordoloi, D.; Khwairakpam, A.D.; Arfuso, F.; Chinnathambi, A.; Alahmadi, T.A.; Alharbi, S.A.; Sethi, G.; Kumar, A.P.; Kunnumakkara, A.B. NGAL is Downregulated in Oral Squamous Cell Carcinoma and Leads to Increased Survival, Proliferation, Migration, and Chemoresistance. Preprints 2018, 2018050076 (doi: 10.20944/preprints201805.0076.v1). Monisha, J.; Roy, N.K.; Padmavathi, G.; Banik, K.; Bordoloi, D.; Khwairakpam, A.D.; Arfuso, F.; Chinnathambi, A.; Alahmadi, T.A.; Alharbi, S.A.; Sethi, G.; Kumar, A.P.; Kunnumakkara, A.B. NGAL is Downregulated in Oral Squamous Cell Carcinoma and Leads to Increased Survival, Proliferation, Migration, and Chemoresistance. Preprints 2018, 2018050076 (doi: 10.20944/preprints201805.0076.v1).

Abstract

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 compared to normal tissues. The downregulation of NGAL was strongly correlated with the degree of differentiation and stage (I-IV), and can serve as a prognostic biomarker for oral cancer. Tobacco carcinogens were also found to be involved in the downregulation of NGAL. Mechanistic studies revealed that knockdown of NGAL increased oral cancer cell proliferation, survival, and migration, and also induced resistance against cisplatin. Silencing of NGAL activated mTOR signaling and reduced autophagy by the LKB1-AMPK-p53-Redd1 signaling axis. Moreover, cyclin-D1, Bcl-2, and 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.

Subject Areas

Oral cancer; mTOR pathway; secreted glycoprotein; drug resistance

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