Cancer research (Chicago, Ill.), 2017-01, Vol.77 (1), p.100-111
2017
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Details
- Autor(en) / Beteiligte
- Titel
- KRAS/NF-κB/YY1/miR-489 Signaling Axis Controls Pancreatic Cancer Metastasis
- Ist Teil von
- Cancer research (Chicago, Ill.), 2017-01, Vol.77 (1), p.100-111
- Ort / Verlag
- United States: American Association for Cancer Research, Inc
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- KRAS activation occurring in more than 90% of pancreatic ductal adenocarcinomas (PDAC) drives progression and metastasis, but the underlying mechanisms involved in these processes are still poorly understood. Here, we show how KRAS acts through inflammatory NF-κB signaling to activate the transcription factor YY1, which represses expression of the tumor suppressor gene miR-489. In PDAC cells, repression of miR-489 by KRAS signaling inhibited migration and metastasis by targeting the extracellular matrix factors ADAM9 and MMP7. miR-489 downregulation elevated levels of ADAM9 and MMP7, thereby enhancing the migration and metastasis of PDAC cells. Together, our results establish a pivotal mechanism of PDAC metastasis and suggest miR-489 as a candidate therapeutic target for their attack. Cancer Res; 77(1); 100-11. ©2016 AACR.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0008-5472eISSN: 1538-7445DOI: 10.1158/0008-5472.CAN-16-1898Titel-ID: cdi_proquest_miscellaneous_1835539469
- Format
- –
- Schlagworte
- Animals, Carcinoma, Pancreatic Ductal - genetics, Carcinoma, Pancreatic Ductal - metabolism, Carcinoma, Pancreatic Ductal - pathology, Cell Line, Tumor, Extracellular matrix, Gene Expression Regulation, Neoplastic - physiology, Heterografts, Humans, Inflammation, K-Ras protein, Matrilysin, Metastases, Metastasis, Mice, Mice, Inbred NOD, Mice, SCID, MicroRNAs - genetics, MicroRNAs - metabolism, Neoplasm Invasiveness - genetics, Neoplasm Invasiveness - pathology, NF-kappa B - genetics, NF-kappa B - metabolism, NF-κB protein, Pancreatic cancer, Pancreatic Neoplasms - genetics, Pancreatic Neoplasms - metabolism, Pancreatic Neoplasms - pathology, Polymerase Chain Reaction, Proto-Oncogene Proteins p21(ras) - genetics, Proto-Oncogene Proteins p21(ras) - metabolism, Signal Transduction - physiology, Transcriptome, Tumor suppressor genes, YY1 protein, YY1 Transcription Factor - genetics, YY1 Transcription Factor - metabolism