An epigenetic switch involving NF-kapaB, Lin28, Let-7 microRNA, and IL6 links inflammation to cell transformation (Cell, 2009, 139:693-706)

報告日期: 2010/03/12
報告時間: 16:00/16:50
報告學生: 盧佳杏
講評老師: 呂佩融
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/990312-2.pdf

An Epigenetic Switch Involving NF-kB, Lin28, Let-7 MicroRNA, and IL6 Links Inflammation to Cell Transformation

Dimitrios Iliopoulos, Heather A. Hirsch, and Kevin Struhl

Cell 139, 693-706, November 13, 2009

 

Speaker: 盧佳杏

Commentator: 呂佩融老師

Date: 2010-03-12

Time: 16:00-16:50

Room: 602

 

Abstract

 

   The association between inflammation and tumorigenesis has been studied intensively in recent years. Accumulating evidence indicates that oncogene activation can trigger intracellular signaling then cause cell transformation. Some microRNAs are emerging as a potential link between inflammation and cancer. However, the mechanism switch between nontransformed and transformed cells still to be further characterized. In this study, the author established an inducible model of oncogenesis in which activate Src by treatment of cell with Tamoxifen (TAM) cause cell forms self-renewing mammospheres and produce inflammation cytokines. Those inflammation response was achieved by NF-κB directly activate Lin28 transcription, therefore rapidly reduces Let-7 microRNA levels. Let-7 down-regulation keeps IL6 appearance. Activation of STAT3 by IL6 is critical for tumor development. On the other hand, depletion of IL6 blocks NF-κB activation point out there is positive feedback to maintain this inflammation situation. Taken together, these data suggest that oncoprotein induce epigenetic switch, turn on inflammation signal pathway in cell. Moreover, the inflammatory regulatory circuit that even in the absence of the inducing signal is maintaining in human cancer. As a consequence, this paradigm could help us to highlights the role of various pro-inflammatory mediators in carcinogenesis. And a therapeutic approach targeting the involved oncogene is expected to partially target pro-tumor inflammation.

 

References

1. Hua Yu, Marcin Kortylewski and Drew Pardoll. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nature Immunology. 2007, 7:41-51.

2. Willscott E Naugler and Michael Karin. NF-κB and cancer - identifying targets and mechanisms. Current Opinion in Genetics & Development. 2008, 18:19-26.

3. Maria Grazia Borrello, Debora Degl’Innocenti, Marco A. Pierotti. Inflammation and cancer: The oncogene-driven connection. Cancer Letters. 2008, 267:262-270.