RNA Sequencing of Pancreatic Circulating Tumour Cells Implicates WNT Signaling in Metastasis

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RNA Sequencing of Pancreatic Circulating Tumour Cells Implicates WNT Signaling in Metastasis

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Title: RNA Sequencing of Pancreatic Circulating Tumour Cells Implicates WNT Signaling in Metastasis
Author: Yu, Min; Ting, David Tsai; Stott, Shannon; Wittner, Ben; Ozsolak, Fatih; Paul, Suchismita; Ciciliano, Jordan C.; Smas, Malgorzata E.; Winokur, Daniel; Gilman, Anna J.; Ulman, Matthew J.; Xega, Kristina; Contino, Gianmarco; Alagesan, Brinda; Brannigan, Brian W.; Milos, Patrice M.; Ryan, David P.; Sequist, Lecia VanDam; Bardeesy, Nabeel; Ramaswamy, Sridhar; Toner, Mehmet; Maheswaran, Shyamala; Haber, Daniel Arie

Note: Order does not necessarily reflect citation order of authors.

Citation: Yu, Min, David T. Ting, Shannon L. Stott, Ben S. Wittner, Fatih Ozsolak, Suchismita Paul, Jordan C. Ciciliano, et al. 2012. RNA sequencing of pancreatic circulating tumour cells implicates WNT signaling in metastasis. Nature 487(7408): 510-513.
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Abstract: Circulating tumour cells (CTCs) shed into blood from primary cancers include putative precursors that initiate distal metastases. While 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 (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 signaling in 5 of 11 cases. Thus, molecular analysis of CTCs may identify candidate therapeutic targets to prevent the distal spread of cancer.
Published Version: doi:10.1038/nature11217
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408856/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10611781
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