Journal article
Twist transcriptionally up-regulates AKT2 in breast cancer cells leading to increased migration, invasion, and resistance to paclitaxel
Cancer research (Chicago, Ill.), Vol.67(5), pp.1979-1987
2007
DOI: 10.1158/0008-5472.CAN-06-1479
PMID: 17332325
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 β1 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.
Details
- Title: Subtitle
- Twist transcriptionally up-regulates AKT2 in breast cancer cells leading to increased migration, invasion, and resistance to paclitaxel
- Creators
- George Z CHENG - Department of Microbiology, Mount Sinai School of Medicine, New York, New York, United StatesJoseph CHAN - Department of Microbiology, Mount Sinai School of Medicine, New York, New York, United StatesQi Wang - Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida College of Medicine, Tampa, Florida, United StatesWEIZHOU ZHANG - Department of Microbiology, Mount Sinai School of Medicine, New York, New York, United StatesCalvin D SUN - Department of Microbiology, Mount Sinai School of Medicine, New York, New York, United StatesLu-Hai WANG - Department of Microbiology, Mount Sinai School of Medicine, New York, New York, United States
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.67(5), pp.1979-1987
- Publisher
- American Association for Cancer Research
- DOI
- 10.1158/0008-5472.CAN-06-1479
- PMID
- 17332325
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 2007
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984083290502771
Metrics
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