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Genes Dev DOI:10.1101/gad.1820109

MicroRNA dynamics in the stages of tumorigenesis correlate with hallmark capabilities of cancer.

Publication TypeJournal Article
Year of Publication2009
AuthorsOlson, P, Lu, J, Zhang, H, Shai, A, Chun, MG, Wang, Y, Libutti, SK, Nakakura, EK, Golub, TR, Hanahan, D
JournalGenes Dev
Date Published2009 Sep 15
KeywordsAngiogenesis Inhibitors, Animals, Cell Differentiation, Cell Proliferation, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Indoles, Mice, Mice, Inbred C57BL, MicroRNAs, Neovascularization, Pathologic, Neuroendocrine Tumors, Pancreatic Neoplasms, Pyrroles, Tumor Cells, Cultured

While altered expression of microRNAs (miRs) in tumors has been well documented, it remains unclear how the miR transcriptome intersects neoplastic progression. By profiling the miR transcriptome we identified miR expression signatures associated with steps in tumorigenesis and the acquisition of hallmark capabilities in a prototypical mouse model of cancer. Metastases and a rare subset of primary tumors shared a distinct miR signature, implicating a discrete lineage for metastatic tumors. The miR-200 family is strongly down-regulated in metastases and met-like primary tumors, thereby relieving repression of the mesenchymal transcription factor Zeb1, which in turn suppresses E-cadherin. Treatment with a clinically approved angiogenesis inhibitor normalized angiogenic signature miRs in primary tumors, while altering expression of metastatic signature miRs similarly to liver metastases, suggesting their involvement in adaptive resistance to anti-angiogenic therapy via enhanced metastasis. Many of the miR changes associated with specific stages and hallmark capabilities in the mouse model are similarly altered in human tumors, including cognate pancreatic neuroendocrine tumors, implying a generality.


Alternate JournalGenes Dev.
PubMed ID19759263
PubMed Central IDPMC2751988
Grant ListT32 CA009043 / CA / NCI NIH HHS / United States
T32 CA09043 / CA / NCI NIH HHS / United States