Alternatively spliced tissue factor promotes breast cancer growth in a β1 integrin-dependent manner.

Abstract:

:Full-length tissue factor (flTF), the coagulation initiator, is overexpressed in breast cancer (BrCa), but associations between flTF expression and clinical outcome remain controversial. It is currently not known whether the soluble alternatively spliced TF form (asTF) is expressed in BrCa or impacts BrCa progression. We are unique in reporting that asTF, but not flTF, strongly associates with both tumor size and grade, and induces BrCa cell proliferation by binding to β1 integrins. asTF promotes oncogenic gene expression, anchorage-independent growth, and strongly up-regulates tumor expansion in a luminal BrCa model. In basal BrCa cells that constitutively express both TF isoforms, asTF blockade reduces tumor growth and proliferation in vivo. We propose that asTF plays a major role in BrCa progression acting as an autocrine factor that promotes tumor progression. Targeting asTF may comprise a previously unexplored therapeutic strategy in BrCa that stems tumor growth, yet does not impair normal hemostasis.

authors

Kocatürk B,Van den Berg YW,Tieken C,Mieog JS,de Kruijf EM,Engels CC,van der Ent MA,Kuppen PJ,Van de Velde CJ,Ruf W,Reitsma PH,Osanto S,Liefers GJ,Bogdanov VY,Versteeg HH

doi

10.1073/pnas.1307100110

subject

Has Abstract

pub_date

2013-07-09 00:00:00

pages

11517-22

issue

28

eissn

0027-8424

issn

1091-6490

pii

1307100110

journal_volume

110

pub_type

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