Gene interactions and pathways from curated databases and text-mining
Oncology 2007, PMID: 18523362

GM3 signals regulating TNF-alpha expression are mediated by Rictor and Arhgdib in mouse melanoma B16 cells.

Wang, Pu; Yang, Xiaoyan; Wu, Peixing; Zhang, Jinghai; Sato, Toshinori; Yamagata, Sadako; Yamagata, Tatsuya

OBJECTIVE

We have previously shown GM3 to positively regulate TNF-alpha expression via a PI3K/Akt pathway in mouse melanoma B16 cells [Wang et al.: Biochem Biophys Res Commun 2007;356:438-443]. The GM3 signal was shown to be located upstream of Akt, but whether it is located upstream of PI3K and which molecule is the effector of PI3K remain to be clarified.

METHODS

We used inhibitors of PI3K and mTOR, and siRNA directed to Rictor, Raptor and Rho-GDP dissociation inhibitor beta (Arhgdib).

RESULTS

PI3K inhibitors LY294002 and LY303511 were shown to suppress TNF-alpha expression that is stimulated by GM3 in B16 cells, suggesting that the GM3 signal is located upstream of the PI3K-Akt pathway. Rapamycin suppressed TNF-alpha expression, indicating mTOR to be involved in the pathway. Either siRNA Raptor or siRNA Rictor suppressed TNF-alpha expression, but the latter suppressed the effects of GM3 on TNF-alpha expression and Akt phosphorylation at Ser(473), indicating the GM3 signal to be transduced via Rictor/mTOR and Akt (Ser(473)), leading to TNF-alpha stimulation. Finally, Arhgdib, the tumor suppressor gene whose expression is associated with GM3, was shown to be upstream of TNF-alpha.

CONCLUSIONS

The GM3 signal is thus transduced in B16 cells through a PI3K, Rictor/mTOR, Akt, Arhgdib pathway, leading to stimulated expression of TNF-alpha.

Diseases/Pathways annotated by Medline MESH: Disease Models, Animal, Melanoma, Experimental
Document information provided by NCBI PubMed

Text Mining Data

TNF-alpha ⊣ Rictor: " Either siRNA Raptor or siRNA Rictor suppressed TNF-alpha expression, but the latter suppressed the effects of GM3 on TNF-alpha expression and Akt phosphorylation at Ser ( 473 ), indicating the GM3 signal to be transduced via Rictor/mTOR and Akt ( Ser ( 473 ) ), leading to TNF-alpha stimulation "

TNF-alpha ⊣ Raptor: " Either siRNA Raptor or siRNA Rictor suppressed TNF-alpha expression, but the latter suppressed the effects of GM3 on TNF-alpha expression and Akt phosphorylation at Ser ( 473 ), indicating the GM3 signal to be transduced via Rictor/mTOR and Akt ( Ser ( 473 ) ), leading to TNF-alpha stimulation "

Akt → Rictor: " Either siRNA Raptor or siRNA Rictor suppressed TNF-alpha expression, but the latter suppressed the effects of GM3 on TNF-alpha expression and Akt phosphorylation at Ser ( 473 ), indicating the GM3 signal to be transduced via Rictor/mTOR and Akt ( Ser ( 473 ) ), leading to TNF-alpha stimulation "

Akt → Raptor: " Either siRNA Raptor or siRNA Rictor suppressed TNF-alpha expression, but the latter suppressed the effects of GM3 on TNF-alpha expression and Akt phosphorylation at Ser ( 473 ), indicating the GM3 signal to be transduced via Rictor/mTOR and Akt ( Ser ( 473 ) ), leading to TNF-alpha stimulation "

Manually curated Databases

No curated data.