Alternatively spliced tissue factor promotes breast cancer growth in a beta 1 integrin-dependent manner


Kocaturk B. , Van den Berg Y. W. , Tiekena C., Mieog J. S. D. , de Kruijf E. M. , Engels C. C. , ...Daha Fazla

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, cilt.110, ss.11517-11522, 2013 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 110 Konu: 28
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1073/pnas.1307100110
  • Dergi Adı: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
  • Sayfa Sayıları: ss.11517-11522

Özet

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 beta 1 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.