Related Experiment Video
Updated: Aug 9, 2026

Quantification of Breast Cancer Cell Invasiveness Using a Three-dimensional (3D) Model
Published on: June 11, 2014
Akt blocks breast cancer cell motility and invasion through the transcription factor NFAT
Merav Yoeli-Lerner1, Gary K Yiu, Isaac Rabinovitz
1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Abstract:
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.
Insights
The study reveals that Akt signaling inhibits breast cancer cell migration and invasion by reducing NFAT levels. Downregulating Akt enhances cancer cell motility, highlighting Akt
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- The phosphoinositide 3-kinase (PI3K) pathway, particularly Akt/PKB, is crucial for cancer cell survival and growth.
- The role of Akt in cancer cell motility, a critical aspect of tumor invasion, remains less understood.
Purpose of the Study:
- To investigate the role of Akt signaling in regulating breast cancer cell migration and invasion.
- To elucidate the molecular mechanisms by which Akt influences cancer cell motility.
Main Methods:
- Utilized RNA interference to downregulate Akt expression in breast cancer cells.
- Assessed the effects of Akt modulation on cell migration and invasion assays.
- Investigated the impact of Akt on the transcriptional activity of NFAT (nuclear factor of activated T cells).
- Examined the role of the E3 ubiquitin ligase HDM2 in Akt-mediated NFAT degradation.
Main Results:
- Activation of Akt significantly inhibited breast cancer cell migration and invasion.
- Downregulation of Akt using RNA interference led to increased cancer cell motility and invasion.
- Akt was found to suppress NFAT transcriptional activity.
- Akt signaling promotes NFAT degradation via HDM2-mediated ubiquitination.
Conclusions:
- Akt signaling acts as a suppressor of breast cancer cell motility and invasion.
- The inhibitory effect of Akt on invasion is partly mediated by the downregulation of NFAT transcriptional activity.
- These findings identify a novel mechanism involving Akt and NFAT in controlling breast cancer cell invasion.
More Related Videos
Related Concept Videos
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Inhibition of Cdk Activity
Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Cancer Cell Migration through Invadopodia
The Intrinsic Apoptotic Pathway

