Title
Constitutively Active Stat3 Enhances Neu-Mediated Migration And Metastasis In Mammary Tumors Via Upregulation Of Cten
Abstract
The transcription factor signal transducer and activator of transcription 3 (STAT3) is constitutively activated in tumors of different origin, but the molecular bases for STAT3 requirement are only partly understood. To evaluate the contribution of enhanced Stat3 activation in a controlled model system, we generated knockin mice wherein a mutant constitutively active Stat3C allele replaces the endogenous wild-type allele. Stat3C could enhance the tumorigenic power of the rat Neu oncogene in mouse mammary tumor virus (MMTV)-Neu transgenic mice, triggering the production of earlier onset, more invasive mammary tumors. Tumor-derived cell lines displayed higher migration, invasion, and metastatic ability and showed disrupted distribution of cell-cell junction markers mediated by Stat3-dependent overexpression of the COOH terminal tensin-like (Cten) focal adhesion protein, which was also significantly upregulated in Stat3C mammary tumors. Importantly, the proinflammatory cytokine interleukin-6 could mediate Cten induction in MCF10 cells in an exquisitely Stat3-dependent way, showing that Cten upregulation is a feature of inflammation-activated Stat3. In light of the emerging pivotal role of Stat3 in connecting inflammation and cancer, our identification of Cten as a Stat3-dependent mediator of migration provides important new insights into the oncogenic role of Stat3, particularly in the breast. ©2010 AACR.
Publication Date
3-15-2010
Publication Title
Cancer Research
Volume
70
Issue
6
Number of Pages
2558-2567
Document Type
Article
Personal Identifier
scopus
DOI Link
https://doi.org/10.1158/0008-5472.CAN-09-2840
Copyright Status
Unknown
Socpus ID
77950211267 (Scopus)
Source API URL
https://api.elsevier.com/content/abstract/scopus_id/77950211267
STARS Citation
Barbieri, Isaia; Pensa, Sara; Pannellini, Tania; Quaglino, Elena; and Maritano, Diego, "Constitutively Active Stat3 Enhances Neu-Mediated Migration And Metastasis In Mammary Tumors Via Upregulation Of Cten" (2010). Scopus Export 2010-2014. 1327.
https://stars.library.ucf.edu/scopus2010/1327