Invasion Hotspot 1.0

一昨日、今年の夏前に書き上げた「Invasion Hotspot」の論文を、bioRxivで公開した。bioRxivのようないわゆるプレプリントサーバを使うのは今回が初めて。夏前に書き上げたときに既に投稿準備は全て終わっていたので、今回の投稿はいくらか基本情報を入力して原稿をアップロードするだけだった。なぜこのタイミングかと言うと、こないだのJDRCで内容を発表したというのもあるけど、一番の理由は科研費の申請書で、既にこの話はちゃんと論文の形にして公開していますよ、というのを示したかったから。まぁ、そのようなことで公開しちゃったという感じなのだが、まだ追加実験も続けていて、良い実験結果が出ればもう少し改訂してからジャーナルに投稿しようと考えている。

Tumor-Cell Invasion Initiates at Invasion Hotspots, an Epithelial Tissue-Intrinsic Microenvironment. bioRxiv doi:10.1101/2021.09.28.462102.

Malignant cancers emerge in epithelial tissues through a progressive process in which a single transformed mutant cell becomes tumorigenic and invasive. Although numerous genes involved in the malignant transformation of cancer cells have been described, how tumor cells launch an invasion into the basal side of epithelial tissues remains elusive. Here, using a Drosophila wing imaginal disc epithelia, we show that genetically mosaic clones of cells mutant for a neoplastic-tumor-suppressor gene (nTSG) in combination with the oncogenic Ras (RasV12) expression initiate invasion into the basal side of the epithelial layer at specific spots in the epithelial tissue. In this "invasion hotspot", the oncogenic double-mutant cells activate c-Jun N-terminal kinase (JNK) signaling, which causes basal extrusion of the double-mutant cells and destruction of basement membrane through upregulation of a matrix metalloprotease, MMP1. Conversely, in other regions of the epithelial tissue, the double-mutant cells do not strongly activate JNK, deviate from the apical side of the epithelial layer, and show benign tumor growth in the lumen. These data indicate that the onset of tumor-cell invasion is highly dependent on the tissue-intrinsic local microenvironment. Given the conservation of genetic signaling pathways involved in this process, initiation of tumor-cell invasion from invasion hotspots in Drosophila wing imaginal epithelia could help us to understand the developmental mechanisms of invasive cancers.