Molecular Cell
Volume 20, Issue 4, 23 November 2005, Pages 539-550
Journal home page for Molecular Cell

Article
Akt Blocks Breast Cancer Cell Motility and Invasion through the Transcription Factor NFAT

https://doi.org/10.1016/j.molcel.2005.10.033Get rights and content
Under an Elsevier user license
open archive

Summary

The phosphoinositide 3-kinase (PI 3-K) signaling axis is intimately associated with deregulated cancer cell growth, primarily by promoting increased survival through Akt/PKB (protein kinase B). However, there is relatively little information on the role of Akt in cancer cell motility, a key phenotype of invasive carcinomas. Here we report that activation of Akt inhibits carcinoma migration and invasion of breast cancer cells. Conversely, downregulation of Akt using RNA interference increased migration and invasion. Akt blunts invasion by inhibiting the transcriptional activity of NFAT (nuclear factor of activated T cells). Specifically, signaling through Akt reduces NFAT expression levels due to ubiquitination and proteasomal degradation, mediated by the E3 ubiquitin ligase HDM2. These results indicate that while Akt can promote tumor progression through increased cell survival mechanisms, it can block breast cancer cell motility and invasion by a mechanism that depends, at least in part, on the NFAT transcription factor.

Cited by (0)