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

    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 [email protected]

    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

    Language

    English

    First Page

    2558

    Last Page

    2567

    WOS Identifier

    WOS:000278485900043

    ISSN

    0008-5472

    Share

    COinS
     

    Accessibility Statement

    This item was created or digitized prior to April 24, 2027, or is a reproduction of legacy media created before that date. It is preserved in its original, unmodified state specifically for research, reference, or historical recordkeeping. In accordance with the ADA Title II Final Rule, the University Libraries provides accessible versions of archival materials upon request. To request an accommodation for this item, please submit an accessibility request form.