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Lipocalin 2 potentially contributes to tumorigenesis from colitis via IL-6/STAT3/NF-κB signaling pathway.
| Content Provider | Europe PMC |
|---|---|
| Author | Kim, Se Lim Shin, Min Woo Seo, Seung Young Kim, Sang Wook |
| Copyright Year | 2022 |
| Abstract | AbstractLipocalin (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. |
| Page Count | 14 |
| ISSN | 01448463 |
| Volume Number | 42 |
| PubMed Central reference number | PMC9109459 |
| Issue Number | 5 |
| PubMed reference number | 35470375 |
| Journal | Bioscience Reports [Biosci. Rep] |
| e-ISSN | 15734935 |
| DOI | 10.1042/BSR20212418 |
| Language | English |
| Publisher | Portland Press Ltd. |
| Publisher Date | 2022-05-01 |
| Access Restriction | Open |
| Rights License | This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY). © 2022 The Author(s). |
| Subject Keyword | Colitis-associated cancer Colorectal cancer Interleukin-6 Lipocalin 2 NF-kB STAT3 |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Molecular Biology Biochemistry Biophysics |
