Oncogenic Ras-induced morphologic change is through MEK/ERK signaling pathway to downregulate stat3 at a posttranslational level in NIH3T3 cells

Hsuan Heng Yeh, Chin Han Wu, Raghavaraju Giri, Ken Kato, Kimitoshi Kohno, Hiroto Izumi, Cheng Yang Chou, Wu Chou Su, Hsiao Sheng Liu

研究成果: Article

15 引文 斯高帕斯(Scopus)


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-ras V12 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.

頁(從 - 到)52-60
出版狀態Published - 2008 一月


All Science Journal Classification (ASJC) codes

  • Cancer Research