2016年9月2日金曜日

THS is out.

日本時間で今日未明、ついに「Tumor Hotspot」の論文がPLOS Biologyで公開された。今回も発表までだいぶ長いことかかったので、やっとこさやなぁという感じはいつもと同じなんだけども、この「腫瘍ホットスポット」というコンセプトが今後どのように広まっていくのか、そしてこれをベースに今後自分の研究がどのように展開していくのか、など色々と楽しみなことは多い。

Epithelial Tumors Originate in Tumor Hotspots, a Tissue-Intrinsic Microenvironment.  PLoS Biology 14(9): e1002537. 
Malignant tumors are caused by uncontrolled proliferation of transformed mutant cells that have lost the ability to maintain tissue integrity. Although a number of causative genetic backgrounds for tumor development have been discovered, the initial steps mutant cells take to escape tissue integrity and trigger tumorigenesis remain elusive. Here, we show through analysis of conserved neoplastic tumor-suppressor genes (nTSGs) in Drosophila wing imaginal disc epithelia that tumor initiation depends on tissue-intrinsic local cytoarchitectures, causing tumors to consistently originate in a specific region of the tissue. In this “tumor hotspot” where cells constitute a network of robust structures on their basal side, nTSG-deficient cells delaminate from the apical side of the epithelium and begin tumorigenic overgrowth by exploiting endogenous Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling activity. Conversely, in other regions, the “tumor coldspot” nTSG-deficient cells are extruded toward the basal side and undergo apoptosis. When the direction of delamination is reversed through suppression of RhoGEF2, an activator of the Rho family small GTPases, and JAK/STAT is activated ectopically in these coldspot nTSG-deficient cells, tumorigenesis is induced. These data indicate that two independent processes, apical delamination and JAK/STAT activation, are concurrently required for the initiation of nTSG-deficient-induced tumorigenesis. Given the conservation of the epithelial cytoarchitecture, tumorigenesis may be generally initiated from tumor hotspots by a similar mechanism.

2 件のコメント:

  1. 論文出版おめでとうございます! 今後の展開が楽しみです

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  2. ありがとうございます! 今後の展開のなかでBonoさんとコラボできたら光栄です。

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