Lipocalin 2 potentially contributes to tumorigenesis from colitis via IL-6/STAT3/NF-κB signaling pathway

Lipocalin (LCN) 2 (LCN2), a member of the lipocalin superfamily, plays an important role in oncogenesis and progression in various types of cancer. However, the role of LCN2 in inflammation-associated cancer remains unknown. Here, we explored the functional role and mechanisms of LCN2 in tumorigenes...

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Bibliographic Details
Published in:Bioscience reports 2022-05, Vol.42 (5), p.1
Main Authors: Kim, Se Lim, Shin, Min Woo, Seo, Seung Young, Kim, Sang Wook
Format: Article
Language:English
Subjects:
Animal models
Animals
Biotechnology
Cancer
Cell activation
Cell culture
Cell growth
Cell survival
Cell Transformation, Neoplastic - genetics
Colitis
Colitis - chemically induced
Colitis - genetics
Colorectal cancer
Colorectal carcinoma
Cytokines
Diagnostics & Biomarkers
Disease prevention
Gene Expression & Regulation
Genes
Immunology & Inflammation
Inflammation
Inflammatory bowel disease
Interleukin 6
Interleukin-6 - genetics
Interleukin-6 - metabolism
Laboratory animals
Lipocalin
Lipocalin-2 - genetics
Lipocalin-2 - metabolism
Mice
Neutrophils
NF-kappa B - genetics
NF-kappa B - metabolism
NF-κB protein
Pathogens
Proteins
Reagents
Signal Transduction
siRNA
Stat3 protein
STAT3 Transcription Factor - genetics
STAT3 Transcription Factor - metabolism
Transcription factors
Tumorigenesis
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Summary:Lipocalin (LCN) 2 (LCN2), a member of the lipocalin superfamily, plays an important role in oncogenesis and progression in various types of cancer. However, the role of LCN2 in inflammation-associated cancer remains unknown. Here, we explored the functional role and mechanisms of LCN2 in tumorigenesis using murine colitis-associated cancer (CAC) models and human colorectal cancer (CRC) cells. Using murine CAC models, we found that LCN2 was preferentially expressed in colonic tissues from CAC models compared with tissues from normal mice. In vitro results demonstrated that the levels of LCN2 mRNA and protein were markedly up-regulated by interleukin (IL) 6 (IL-6) in human CRC cells. Interestingly, we found LCN2 up-regulation by IL-6 is diminished by nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) inhibition using specific inhibitors and small interfering RNA (siRNA). Reporter assay results determined that IL-6 induces LCN2 gene promoter activity under control of NF-κB/STAT3 activation. IL-6-induced LCN2 regulated cell survival and susceptibility of developmental factors to the NF-κB/STAT3 pathway. Taken together, our results highlight the unknown role of LCN2 in CAC progression and suggest that increased LCN2 may serve as an indicator of CRC development in the setting of chronic inflammation.
ISSN:0144-8463
1573-4935
DOI:10.1042/BSR20212418