Implication and role of neutrophil gelatinase-associated lipocalin in cancer: lipocalin-2 as a potential novel emerging comprehensive therapeutic target for a variety of cancer types

Abstract

Cancer is a leading cause of mortalities worldwide. Over the past few decades, exploration of molecular mechanisms behind cancer initiation and progression has been of great interest in the viewpoint of both basic and clinical scientists. It is generally believed that identification of key molecules implicated in cancer pathology not only improves our understanding of the disease, but also could result in introduction of novel therapeutic strategies. Neutrophil gelatinase-associated lipocalin (NGAL)/lipocalin-2 (LCN2) is a member of lipocalin superfamily with a variety of functions. Although the main function of LCN2 is still unknown, many studies confirmed its significant role in the initiation, progression, and metastasis of various types of cancer. Furthermore, aberrant expression of LCN2 is also concerned with the chemo- and radio-resistant phenotypes of tumors. Here, we will review the contribution of known functions of LCN2 to the pathophysiology of cancer. We also highlight how the deregulated expression of LCN2 is associated with a variety of fatal types of cancer for which there are no effective therapeutic modalities. The unique and multiple functions of LCN2 and its widespread expression in different types of cancer prompted us to suggest LCN2 could be considered either as a valuable diagnostic and prognostic biomarker or as a potential novel therapeutic target.