Publication Date:
2012-07-06
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408856/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408856/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, Min -- Ting, David T -- Stott, Shannon L -- Wittner, Ben S -- 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 V -- Bardeesy, Nabeel -- Ramaswamy, Sridhar -- Toner, Mehmet -- Maheswaran, Shyamala -- Haber, Daniel A -- 5K12CA87723-09/CA/NCI NIH HHS/ -- 5R01EB008047/EB/NIBIB NIH HHS/ -- CA129933/CA/NCI NIH HHS/ -- P01 CA117969/CA/NCI NIH HHS/ -- R01 CA129933/CA/NCI NIH HHS/ -- U01 EB012493/EB/NIBIB NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Jul 26;487(7408):510-3. doi: 10.1038/nature11217.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22763454" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Survival
;
Contact Inhibition
;
Disease Models, Animal
;
Gene Expression Regulation, Neoplastic/*genetics
;
Genes, Neoplasm/genetics
;
Humans
;
MAP Kinase Kinase Kinases/antagonists & inhibitors
;
Mice
;
Neoplasm Metastasis/*genetics
;
Neoplastic Cells, Circulating/*metabolism
;
Pancreatic Neoplasms/*genetics/*pathology
;
RNA, Messenger/analysis/biosynthesis
;
Sequence Analysis, RNA
;
Wnt Proteins/genetics/*metabolism
;
Wnt Signaling Pathway/*genetics
;
Wnt2 Protein/genetics/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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