GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

TableEdit

Jump to: navigation, search

PMID:17332325

You don't have sufficient rights on this wiki to edit tables. Perhaps you need to log in. Changes you make in the Table editor will not be saved back to the wiki

See Help for Help on this wiki. See the documentation for how to use the table editor

Citation

Cheng, GZ, Chan, J, Wang, Q, Zhang, W, Sun, CD and Wang, LH (2007) Twist transcriptionally up-regulates AKT2 in breast cancer cells leading to increased migration, invasion, and resistance to paclitaxel. Cancer Res. 67:1979-87

Abstract

Metastasis, the cardinal feature of malignant tumors, is an important clinical variable in patient prognosis. To understand the basis for metastasis, we systematically selected for highly invasive cells from breast cancer cell lines, MCF7 and MDA-MB-453, with moderate to low invasive ability using Boyden chamber invasion assay. The four-cycle selected invasive lines, named MCF7-I4 and MDA-MB-453-I4, respectively, displayed epithelial-mesenchymal transition (EMT) and dramatically enhanced invasive ability. EMT changes were corroborated with decreased level of E-cadherin and increased vimentin, fibronectin, and beta(1) integrin. Twist, a basic helix-loop-helix transcription factor, and AKT2, a known proto-oncogene, were found to be elevated in the invasive cells compared with the parental. Ectopic expression and knockdown of Twist by short interference RNA resulted in significant increase and reduction, respectively, of AKT2 protein and mRNA expression. Twist bound to E-box elements on AKT2 promoter and enhanced its transcriptional activity. Moreover, silencing AKT2 decreased Twist-promoted migration, invasion, and paclitaxel resistance. Reintroducing AKT2 largely rescued the phenotype resulted from knockdown of Twist in I4 cells, suggesting that AKT2 is a downstream target and functional mediator of Twist. Finally, we observed a 68.8% correlation of elevated Twist and AKT2 expression in late-stage breast cancers as oppose to 13% in early-stage breast cancers. Our study identifies Twist as a positive transcriptional regulator of AKT2 expression, and Twist-AKT2 signaling is involved in promoting invasive ability and survival of breast cancer cells.

Links

PubMed Online version:10.1158/0008-5472.CAN-06-1479

Keywords

Antineoplastic Agents, Phytogenic/pharmacology; Antineoplastic Agents, Phytogenic/therapeutic use; Breast Neoplasms/drug therapy; Breast Neoplasms/genetics; Breast Neoplasms/metabolism; Breast Neoplasms/pathology; Cell Movement/drug effects; Drug Resistance, Neoplasm/drug effects; Gene Expression Regulation, Neoplastic/drug effects; Humans; Neoplasm Invasiveness; Nuclear Proteins/antagonists & inhibitors; Nuclear Proteins/metabolism; Nuclear Proteins/physiology; Paclitaxel/pharmacology; Paclitaxel/therapeutic use; Promoter Regions, Genetic; Proto-Oncogene Proteins c-akt/genetics; Proto-Oncogene Proteins c-akt/metabolism; RNA, Small Interfering/pharmacology; Transcriptional Activation; Tumor Cells, Cultured; Twist Transcription Factor/antagonists & inhibitors; Twist Transcription Factor/metabolism; Twist Transcription Factor/physiology

public



Cancel