RNA sequencing of pancreatic circulating tumour cells implicates WNT signalling in metastasis
| Autor: | Brinda Alagesan, Daniel A. Haber, Malgorzata E. Smas, David P. Ryan, Suchismita Paul, Gianmarco Contino, Nabeel Bardeesy, Min Yu, Brian W. Brannigan, Sridhar Ramaswamy, Fatih Ozsolak, Patrice M. Milos, Ben S. Wittner, Jordan C. Ciciliano, Mehmet Toner, David T. Ting, Daniel Winokur, Kristina Xega, Matthew J. Ulman, Anna J. Gilman, Lecia V. Sequist, Shannon L. Stott, Shyamala Maheswaran |
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| Rok vydání: | 2012 |
| Předmět: |
Cell Survival
Wnt2 Protein Biology Article Metastasis Mice 03 medical and health sciences 0302 clinical medicine Circulating tumor cell WNT2 Pancreatic cancer medicine Animals Humans Anoikis RNA Messenger Neoplasm Metastasis Wnt Signaling Pathway 030304 developmental biology 0303 health sciences Multidisciplinary Contact Inhibition Sequence Analysis RNA Wnt signaling pathway Cancer MAP Kinase Kinase Kinases Neoplastic Cells Circulating medicine.disease Molecular biology 3. Good health Gene Expression Regulation Neoplastic Pancreatic Neoplasms Wnt Proteins Disease Models Animal 030220 oncology & carcinogenesis Cancer research Genes Neoplasm |
| Zdroj: | Nature |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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