Research press release


Nature Cell Biology

Feeding back on tumour initiation


miR200ファミリーに属する低分子RNAは、ZEB1の働きを直接的に阻害して、一部のがん組織からの細胞の浸潤と移動を抑えることが以前に報告されている。一方ZEB1は、miR200の発現を抑制する。今回T Brabletzたちは、miR200が、幹細胞の特性を維持するために必要な、自己複製、増殖や分化抑制などを促進するさまざまの因子も阻害することを明らかにした。彼らはまた、ヒト膵臓がん細胞系列でZEB1が失われると、幹細胞因子のmiR200に依存した阻害により、腫瘍形成開始能が低下することも実証している。また彼らは、マウスおよびヒトに由来する原発巣膵臓がん組織を調べて、分化程度の低い腫瘍ではZEB1と幹細胞因子の発現レベルが高く、それに対して、膵臓がんの長期生存患者から単離された腫瘍ではZEB1のレベルが低いことも明らかにした。


The protein ZEB1 ― which is known to promote invasiveness of epithelial tumours ― also influences the tumour initiating capacity of pancreatic and colorectal cancer cells, and could possibly promote cancerous cells proliferation once they have reached a new organ. The finding, published online this week in Nature Cell Biology, suggests that targeting a feedback loop in which ZEB1 is involved in might represent a promising avenue for the treatment of certain cancers.

The small RNAs of the miR200 family were previously reported to inhibit cell invasion and movement of certain cancerous tissues via direct inhibition of ZEB1. ZEB1 in turn suppresses the expression of miR200. Thomas Brabletz and colleagues now show that miR200 also inhibits various factors required for the maintenance of stem cells characteristics, including factors that promote self-renewal, proliferation and inhibit differentiation. They also demonstrate that loss of ZEB1 in human pancreatic cancer cell lines reduces their tumour initiation potential by suppressing miR200-dependent inhibition of stem cells factors. By examining primary pancreatic cancer tissues of mouse and human origins, they show that less differentiated tumours express high levels of ZEB1 and stem cell factors, while tumours isolated from patients that are long term survivors of pancreatic cancers have low ZEB1.

This study suggests that ZEB1 promotes both tumour spread and initiation by enhancing the stem cells characteristics of the cells that migrate away from the primary tumour to form metastases.

doi: 10.1038/ncb1998


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