Collective cell migration and metastases induced by an epithelial-to-mesenchymal transition in Drosophila intestinal tumors

被引:71
作者
Campbell, Kyra [1 ]
Rossi, Fabrizio [2 ]
Adams, Jamie [1 ]
Pitsidianaki, Ioanna [1 ]
Barriga, Francisco M. [3 ]
Garcia-Gerique, Laura [4 ]
Batlle, Eduard [2 ,5 ]
Casanova, Jordi [2 ,6 ]
Casali, Andreu [7 ]
机构
[1] Univ Sheffield, Bateson Ctr, Dept Biomed Sci, Sheffield S10 2TN, S Yorkshire, England
[2] Barcelona Inst Sci & Technol, Inst Res Biomed IRB Barcelona, Baldiri Reixac 10, Barcelona 08028, Spain
[3] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA
[4] Fundacio St Joan de Deu, Dev Tumor Biol Lab, Hosp St Joan de Deu, Barcelona 08950, Spain
[5] ICREA, Barcelona 08010, Spain
[6] CSIC, IBMB, Baldiri Reixac 10, E-08028 Barcelona, Spain
[7] Fundacio Dr Pifarre IRBLleida, Inst Recerca Biomed Lleida, Lleida 25198, Spain
基金
英国惠康基金;
关键词
CANCER METASTASIS; STEM-CELLS; E-CADHERIN; EMT; PLASTICITY; COLONIZATION; EXPRESSION; MOVEMENT; SURVIVAL; GROWTH;
D O I
10.1038/s41467-019-10269-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Metastasis underlies the majority of cancer-related deaths yet remains poorly understood due, in part, to the lack of models in vivo. Here we show that expression of the EMT master inducer Snail in primary adult Drosophila intestinal tumors leads to the dissemination of tumor cells and formation of macrometastases. Snail drives an EMT in tumor cells, which, although retaining some epithelial markers, subsequently break through the basal lamina of the midgut, undergo a collective migration and seed polyclonal metastases. While metastases re-epithelialize over time, we found that early metastases are remarkably mesenchymal, discarding the requirement for a mesenchymal-to-epithelial transition for early stages of metastatic growth. Our results demonstrate the formation of metastases in adult flies, and identify a key role for partial-EMTs in driving it. This model opens the door to investigate the basic mechanisms underlying metastasis, in a powerful in vivo system suited for rapid genetic and drug screens.
引用
收藏
页数:10
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