title: Lipocalin 2 in cancer: when good immunity goes bad.
abstract: The innate immune molecule Lipocalin 2 (LCN2) was initially shown to combat bacterial infection by binding bacterial siderophores, hence impairing microbial iron sequestration. In recent years, it has become apparent that LCN2 is over-expressed in cancers of diverse histological origin and that it facilitates tumorigenesis by promoting survival, growth, and metastasis. Herein, we discuss emerging evidence that substantiates two functional roles for LCN2 in cancer: promotion of the epithelial-to-mesenchymal transition (EMT) that facilitates an invasive phenotype and metastasis, and sequestration of iron that results in cell survival and tumorigenesis. Further, we present evidence that upregulated LCN2 expression in solid tumors is induced by hypoxia and pro-inflammation, microenvironmental noxae that converge to cause an endoplasmic reticulum (ER) stress response. Taken together, it appears that tumor cells exploit the beneficial innate immune function of LCN2 to support uncontrolled growth. This duplicity in function highlights LCN2 and its upstream driver, the ER stress response, as key targets for cancer therapy.
authors.affiliation: The Laboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0815, United States.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Rodvold
authors.forename: Navin R
authors.initials: NR
authors.lastname: Mahadevan
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zanetti
mesh_terms: D000209:Acute-Phase Proteins / Q000276:immunology; D000818:Animals; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D015513:Oncogene Proteins / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000276:immunology
chemical_list: D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; C071332:Lcn2 protein, mouse