title: RNA sequencing of pancreatic circulating tumour cells implicates WNT signalling in metastasis.
abstract: Circulating tumour cells (CTCs) shed into blood from primary cancers include putative precursors that initiate distal metastases. 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 for efficient capture of CTCs from an endogenous mouse pancreatic cancer model and subjected CTCs to single-molecule RNA sequencing, 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.
authors: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors: Min
authors: M
authors: Yu
authors: David T
authors: DT
authors: Ting
authors: Shannon L
authors: SL
authors: Stott
authors: Ben S
authors: BS
authors: Wittner
authors: Fatih
authors: F
authors: Ozsolak
authors: Suchismita
authors: S
authors: Paul
authors: Jordan C
authors: JC
authors: Ciciliano
authors: Malgorzata E
authors: ME
authors: Smas
authors: Daniel
authors: D
authors: Winokur
authors: Anna J
authors: AJ
authors: Gilman
authors: Matthew J
authors: MJ
authors: Ulman
authors: Kristina
authors: K
authors: Xega
authors: Gianmarco
authors: G
authors: Contino
authors: Brinda
authors: B
authors: Alagesan
authors: Brian W
authors: BW
authors: Brannigan
authors: Patrice M
authors: PM
authors: Milos
authors: David P
authors: DP
authors: Ryan
authors: Lecia V
authors: LV
authors: Sequist
authors: Nabeel
authors: N
authors: Bardeesy
authors: Sridhar
authors: S
authors: Ramaswamy
authors: Mehmet
authors: M
authors: Toner
authors: Shyamala
authors: S
authors: Maheswaran
authors: Daniel A
authors: DA
authors: Haber
mesh_terms: D000818:Animals; D002470:Cell Survival; D003260:Contact Inhibition; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors; D051379:Mice; D009362:Neoplasm Metastasis / Q000235:genetics*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D017423:Sequence Analysis, RNA; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051154:Wnt2 Protein / Q000235:genetics / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D020930:MAP Kinase Kinase Kinases; D012333:RNA, Messenger; D051153:Wnt Proteins; D051154:Wnt2 Protein; D000099151:MAP Kinase Kinase Kinase 7; C495244:WNT2 protein, human