Journal article
Twist Is Transcriptionally Induced by Activation of STAT3 and Mediates STAT3 Oncogenic Function
The Journal of biological chemistry, Vol.283(21), pp.14665-14673
05/23/2008
DOI: 10.1074/jbc.M707429200
PMCID: PMC2386910
PMID: 18353781
Abstract
To explore the basis of metastasis, we compared the human breast cancer lines MCF-7 and MDA-MB453, which have low invasive ability, with their sublines MCF7-I4 and MDA-MB453-I4 with high invasive ability for gene expression and signaling pathways. We previously showed that the I4 lines had dramatically elevated levels of Twist compared with their parental lines. In this study, we observed significantly increased STAT3 Tyr705 phosphorylation, but not the STAT3 protein levels, in the I4 lines. Activation of STAT3 by interleukin-6 or expression of activated Src induced Twist expression at protein and mRNA levels. Inhibiting STAT3 by a small molecule inhibitor, JSI-124, STAT3 small hairpin RNAs, or dominant negative STAT3 resulted in significant reduction of Twist protein and mRNA expression. STAT3 directly bound to the second proximal STAT3-binding site on the human Twist promoter and activated its transcriptional activity. Inhibition of STAT3 reduced migration, invasion, and colony formation of the I4 cells. Ectopic expression of Twist significantly rescued those phenotypes. Ten normal and 46 tumor specimens of breast tissues were examined for activation of STAT3 and expression of Twist. There was a strong correlation between Tyr705 p-STAT3 and Twist level in the late stage tumor tissues. Our results indicate that activated STAT3 transcriptionally induces Twist, which plays an important role in promoting migration, invasion, and anchorage-independent growth. Together with our previous observation that Twist transcriptionally induces AKT2 to mediate Twist-promoted oncogenic functions, we conclude that STAT3, Twist, and AKT2 form a functional signaling axis to regulate pivotal oncogenic properties of cancer cells.
Details
- Title: Subtitle
- Twist Is Transcriptionally Induced by Activation of STAT3 and Mediates STAT3 Oncogenic Function
- Creators
- George Z Cheng - Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029WeiZhou Zhang - Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029Mei Sun - Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612Qi Wang - Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612Domenico Coppola - Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612Mena Mansour - Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029LiMei Xu - Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029Carliann Costanzo - Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029Jin Q Cheng - Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612Lu-Hai Wang - Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.283(21), pp.14665-14673
- DOI
- 10.1074/jbc.M707429200
- PMID
- 18353781
- PMCID
- PMC2386910
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Elsevier Inc
- Grant note
- Grants CA29339 / National Institutes of Health
- Language
- English
- Date published
- 05/23/2008
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984083286302771
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