Lipocalin-2 expression and function in pancreatic diseases

Gumpper, Kristyn; Dangel, Andrew W.; Pita-Grisanti, Valentina; Krishna, Somashekar G.; Lara, Luis F.; Mace, Thomas A.; Papachristou, Georgios I.; Conwell, Darwin L.; Hart, Phil A.; Cruz‐Monserrate, Zobeida

doi:10.1016/j.pan.2020.01.002

Cited by 19 publications

(20 citation statements)

References 82 publications

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“…An interrogation of The Cancer Genome Atlas (TCGA) data portal showed that several cancers have significantly altered expression of LCN2 compared to normal tissue, suggesting LCN2's potential as a prognostic biomarker [39] (Figure 1). Some studies have correlated upregulated LCN2 expression in tumor tissue with poor outcomes caused by increased growth of cancer cells, therapeutic resistance, invasion, and metastasis [27,28,36,40,41]. Similarly, Bauer et al analyzed 207 well-characterized breast cancer tumor tissues by IHC and observed a significant correlation between high LCN2 levels and negative estrogen receptor expression [36].…”

Section: Lcn2 Expression In Cancermentioning

confidence: 99%

Biological Functions and Therapeutic Potential of Lipocalin 2 in Cancer

Santiago-Sánchez

Pita-Grisanti

Quiñones-Díaz

et al. 2020

IJMS

Self Cite

110

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Lipocalin-2 (LCN2) is a secreted glycoprotein linked to several physiological roles, including transporting hydrophobic ligands across cell membranes, modulating immune responses, maintaining iron homeostasis, and promoting epithelial cell differentiation. Although LNC2 is expressed at low levels in most human tissues, it is abundant in aggressive subtypes of cancer, including breast, pancreas, thyroid, ovarian, colon, and bile duct cancers. High levels of LCN2 have been associated with increased cell proliferation, angiogenesis, cell invasion, and metastasis. Moreover, LCN2 modulates the degradation, allosteric events, and enzymatic activity of matrix metalloprotease-9, a metalloprotease that promotes tumor cell invasion and metastasis. Hence, LCN2 has emerged as a potential therapeutic target against many cancer types. This review summarizes the most relevant findings regarding the expression, biological roles, and regulation of LCN2, as well as the proteins LCN2 interacts with in cancer. We also discuss the approaches to targeting LCN2 for cancer treatment that are currently under investigation, including the use of interference RNAs, antibodies, and gene editing.

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Section: Lcn2 Expression In Cancermentioning

confidence: 99%

Biological Functions and Therapeutic Potential of Lipocalin 2 in Cancer

Santiago-Sánchez

Pita-Grisanti

Quiñones-Díaz

et al. 2020

IJMS

Self Cite

110

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“…Elevated LCN2 levels are typically found in obese humans and mouse models of obesity [125,126]. LCN2 has been implicated in the pathogenesis of various pancreatic diseases, including PDAC, acute and chronic pancreatitis, and T2DM [127]. LCN2 is upregulated in PDAC mouse models, correlates to decreased food intake, and its absence protects from tumor cachexia, presumably via a type 4 melanocortin receptor-mediated mechanism [128].…”

Section: Lipocalin-2mentioning

confidence: 99%

Obesity and Pancreatic Cancer: Insight into Mechanisms

Eibl

2021

Cancers

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The prevalence of obesity in adults and children has dramatically increased over the past decades. Obesity has been declared a chronic progressive disease and is a risk factor for a number of metabolic, inflammatory, and neoplastic diseases. There is clear epidemiologic and preclinical evidence that obesity is a risk factor for pancreatic cancer. Among various potential mechanisms linking obesity with pancreatic cancer, the adipose tissue and obesity-associated adipose tissue inflammation play a central role. The current review discusses selected topics and mechanisms that attracted recent interest and that may underlie the promoting effects of obesity in pancreatic cancer. These topics include the impact of obesity on KRAS activity, the role of visceral adipose tissue, intrapancreatic fat, adipose tissue inflammation, and adipokines on pancreatic cancer development. Current research on lipocalin-2, fibroblast growth factor 21, and Wnt5a is discussed. Furthermore, the significance of obesity-associated insulin resistance with hyperinsulinemia and obesity-induced gut dysbiosis with metabolic endotoxemia is reviewed. Given the central role that is occupied by the adipose tissue in obesity-promoted pancreatic cancer development, preventive and interceptive strategies should be aimed at attenuating obesity-associated adipose tissue inflammation and/or at targeting specific molecules that mechanistically link adipose tissue with pancreatic cancer in obese patients.

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“…Then, GO and REACTOME pathway analyses were used to investigate the interactions of these DEGs. Increasing evidence shows that LAPTM4B [52], CEACAM6 [53], SERPINE2 [54] and VNN1 [55], SPHK1 [56], HRG (histidine rich glycoprotein) [57], VEGFC (vascular endothelial growth factor C) [58], ANXA3 [59], APOA2 [60], LCN2 [61], TIMP1 [62], CD63 [63], CD151 [64], MAL2 [65], ARNTL2 [66], PKD2 [67], E2F1 [68], MMP1 [69], CCR7 [70], NOTCH2 [71], BTLA (B and T lymphocyte associated) [72], TFRC (transferrin receptor) [73], CD4 [74], ATM (ATM serine/threonine kinase) [75], LEF1 [76], CSF1R [77], CTSB (cathepsin B) [78], DUSP2 [79] and NR4A1 [80] are closely associated with progression of PDAC. PTGER3 [81] and MAGI2 [82] are linked with angiogenesis, chemoresistance, cell proliferation and migration in ovary cancer, but these genes might be liable for growth PDAC.…”

Section: Discussionmentioning

confidence: 99%

Identification and Interaction Analysis of Molecular Markers in Pancreatic Ductal Adenocarcinoma by Integrated Bioinformatics Analysis and Molecular Docking Experiments

Vastrad¹,

Vastrad²,

Tengli

2020

Preprint

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The current investigation aimed to mine therapeutic molecular targets that play an key part in the advancement of pancreatic ductal adenocarcinoma (PDAC). The expression profiling by high throughput sequencing dataset profile GSE133684 dataset was downloaded from the Gene Expression Omnibus (GEO) database. Limma package of R was used to identify differentially expressed genes (DEGs). Functional enrichment analysis of DEGs were performed. Protein-protein interaction (PPI) networks of the DEGs were constructed. An integrated gene regulatory network was built including DEGs, microRNAs (miRNAs), and transcription factors. Furthermore, consistent hub genes were further validated. Molecular docking experiment was conducted. A total of 463 DEGs (232 up regulated and 231 down regulated genes) were identified between very early PDAC and normal control samples. The results of Functional enrichment analysis revealed that the DEGs were significantly enriched in vesicle organization, secretory vesicle, protein dimerization activity, lymphocyte activation, cell surface, transferase activity, transferring phosphorus-containing groups, hemostasis and adaptive immune system. The PPI network and gene regulatory network of up regulated genes and down regulated genes were established, and hub genes were identified. The expression of hub genes (CCNB1, FHL2, HLA-DPA1 and TUBB1) were also validated to be differentially expressed among PDAC and normal control samples. Molecular docking experiment predicted the novel inhibitory molecules for CCNB1 and FHL2. The identification of hub genes in PDAC enhances our understanding of the molecular mechanisms underlying the progression of this disease. These genes may be potential diagnostic biomarkers and/or therapeutic molecular targets in patients with PDAC.

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Lipocalin-2 expression and function in pancreatic diseases

Cited by 19 publications

References 82 publications

Biological Functions and Therapeutic Potential of Lipocalin 2 in Cancer

Biological Functions and Therapeutic Potential of Lipocalin 2 in Cancer

Obesity and Pancreatic Cancer: Insight into Mechanisms

Identification and Interaction Analysis of Molecular Markers in Pancreatic Ductal Adenocarcinoma by Integrated Bioinformatics Analysis and Molecular Docking Experiments

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