Title

Constitutively Active Stat3 Enhances Neu-Mediated Migration and Metastasis in Mammary Tumors via Upregulation of Cten

Authors

Authors

I. Barbieri; S. Pensa; T. Pannellini; E. Quaglino; D. Maritano; M. Demaria; A. Voster; J. Turkson; F. Cavallo; C. J. Watson; P. Provero; P. Musiani;V. Poli

Comments

Authors: contact us about adding a copy of your work at STARS@ucf.edu

Abbreviated Journal Title

Cancer Res.

Keywords

ANCHORAGE-INDEPENDENT GROWTH; MESSENGER-RNA EXPRESSION; HUMAN; BREAST-CANCER; EPITHELIAL-CELLS; SIGNAL TRANSDUCER; GENE-EXPRESSION; ACTIVATION; PROGRESSION; ONCOGENE; TUMORIGENESIS; Oncology

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 knock-in 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. Cancer Res; 70(6); 2558-67. (C)2010 AACR.

Journal Title

Cancer Research

Volume

70

Issue/Number

6

Publication Date

1-1-2010

Document Type

Article

DOI Link

http://dx.doi.org/10.1158/0008-5472.can-09-2840

Language

English

First Page

2558

Last Page

2567

WOS Identifier

WOS:000278485900043

ISSN

0008-5472

Recommended Citation

"Constitutively Active Stat3 Enhances Neu-Mediated Migration and Metastasis in Mammary Tumors via Upregulation of Cten" (2010). Faculty Bibliography 2010s. 6974.
https://stars.library.ucf.edu/facultybib2010/6974