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Oncogenic Ras-Induced Morphologic Change Is through MEK/ERK Signaling Pathway to Downregulate Stat3 at a Posttranslational Level in NIH3T3 Cells
- Source :
- Neoplasia: An International Journal for Oncology Research, Vol 10, Iss 1, Pp 52-60 (2008)
- Publication Year :
- 2008
- Publisher :
- Elsevier, 2008.
-
Abstract
- Ras is a key regulator of the MAP kinase-signaling cascade and may cause morphologic change of Ras-transformed cells. Signal transducer and activator of transcription 3 (Stat3) can be activated by cytokine stimulation. In this study, we unravel that Ha-rasV12 overexpression can downregulate the expression of Stat3 protein at a posttranslational level in NIH3T3 cells. Furthermore, we demonstrate that Stat3 expression downregulated by Ha-rasV12 overexpression is through proteosome degradation and not through a mTOR/p70S6K-related signaling pathway. The suppression of Stat3 accompanied by the morphologic change induced by Ha-rasV12 was through mitogen extracellular kinase (MEK)/extracellular-regulated kinase (ERK) signaling pathway. Microtubule disruption is involved in Ha-rasV12-induced morphologic change, which could be reversed by overexpression of Stat3. Taken together, we are the first to demonstrate that Stat3 protein plays a critical role in Ha-rasV12-induced morphologic change. Oncogenic Ras-triggered morphologic change is through the activation of MEK/ERK to posttranslationally downregulate Stat3 expression. Our finding may shed light on developing novel therapeutic strategies against Ras-related tumorigenesis.
- Subjects :
- Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Subjects
Details
- Language :
- English
- ISSN :
- 14765586 and 15228002
- Volume :
- 10
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Neoplasia: An International Journal for Oncology Research
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.38ab6e043a5d4f4889e508888bc773a4
- Document Type :
- article
- Full Text :
- https://doi.org/10.1593/neo.07691