RNA sequencing of pancreatic circulating tumour cells implicates WNT signalling in metastasis

被引：396

作者：

Yu, Min ^{[1
,2
,3
,4
]}

Ting, David T. ^{[1
,2
,3
]}

Stott, Shannon L. ^{[1
,2
,3
]}

Wittner, Ben S. ^{[1
,2
,3
]}

Ozsolak, Fatih ^{[5
]}

Paul, Suchismita ^{[1
,2
,3
]}

Ciciliano, Jordan C. ^{[1
,2
,3
]}

Smas, Malgorzata E. ^{[1
,2
,3
]}

Winokur, Daniel ^{[1
,2
,3
]}

Gilman, Anna J. ^{[1
,2
,3
]}

Ulman, Matthew J. ^{[1
,2
,3
]}

Xega, Kristina ^{[1
,2
,3
]}

Contino, Gianmarco ^{[1
,2
,3
]}

Alagesan, Brinda ^{[1
,2
,3
]}

Brannigan, Brian W. ^{[1
,2
,3
]}

Milos, Patrice M. ^{[5
]}

Ryan, David P. ^{[1
,2
,3
]}

Sequist, Lecia V. ^{[1
,2
,3
]}

Bardeesy, Nabeel ^{[1
,2
,3
]}

Ramaswamy, Sridhar ^{[1
,2
,3
]}

Toner, Mehmet ^{[1
,2
,3
]}

Maheswaran, Shyamala ^{[1
,2
,3
]}

Haber, Daniel A. ^{[1
,2
,3
,4
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Canc, Ctr Engn Med, Boston, MA 02114 USA

[2] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA

[3] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA

[4] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

[5] Helicos BioSci Corp, Cambridge, MA 02139 USA

来源：

NATURE | 2012年 / 487卷 / 7408期

关键词：

STEM-CELL; TRANSCRIPTOME; PATHWAY;

D O I：

10.1038/nature11217

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：

Circulating tumour cells (CTCs) shed into blood from primary cancers include putative precursors that initiate distal metastases(1). Although these cells are extraordinarily rare, they may identify cellular pathways contributing to the blood-borne dissemination of cancer. Here, we adapted a microfluidic device(2) for efficient capture of CTCs from an endogenous mouse pancreatic cancer model(3) and subjected CTCs to single-molecule RNA sequencing(4), identifying Wnt2 as a candidate gene enriched in CTCs. Expression of WNT2 in pancreatic cancer cells suppresses anoikis, enhances anchorage-independent sphere formation, and increases metastatic propensity in vivo. This effect is correlated with fibronectin upregulation and suppressed by inhibition of MAP3K7 (also known as TAK1) kinase. In humans, formation of non-adherent tumour spheres by pancreatic cancer cells is associated with upregulation of multiple WNT genes, and pancreatic CTCs revealed enrichment for WNT signalling in 5 out of 11 cases. Thus, molecular analysis of CTCs may identify candidate therapeutic targets to prevent the distal spread of cancer.

引用

页码：510 / U130

页数：6

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