Journal article
Trop-2 promotes prostate cancer metastasis by modulating β1 integrin functions
Cancer research (Chicago, Ill.), v 73(10), pp 3155-3167
15 May 2013
PMID: 23536555
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The molecular mechanisms underlying metastatic dissemination are still not completely understood. We have recently shown that β
1
integrin-dependent cell adhesion to fibronectin (FN) and signaling are affected by a transmembrane molecule, Trop-2, which is frequently upregulated in human carcinomas. Here we report that Trop-2 promotes metastatic dissemination of prostate cancer cells in vivo and is abundantly expressed in metastasis from human prostate cancer. We also show here that Trop-2 promotes prostate cancer cell migration on FN, a phenomenon dependent on β
1
integrins. Mechanistically, we demonstrate that Trop-2 and the α
5
β
1
integrin associate through their extracellular domains, causing relocalization of α
5
β
1
and the β
1
-associated molecule talin from focal adhesions to the leading edges. Trop-2 effect is specific since this molecule does not modulate migration on vitronectin (VN), does not associate with the major VN receptor, α
v
β
3
integrin, and does not affect localization of α
v
β
3
integrin as well as vinculin in focal adhesions. We show that Trop-2 enhances directional prostate cancer cell migration, through modulation of Rac1 GTPase activity. Finally, we demonstrate that Trop-2 induces activation of PAK4, a kinase that has been reported to mediate cancer cell migration. In conclusion, we provide the first evidence that β
1
integrin-dependent migratory and metastatic competence of prostate cancer cells is enhanced by Trop-2.
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Details
- Title
- Trop-2 promotes prostate cancer metastasis by modulating β1 integrin functions
- Creators
- Marco Trerotola - Prostate Cancer Discovery and Development Program, Department of Cancer Biology, Philadelphia, PennsylvaniaDanielle L Jernigan - Department of Pharmacology and Physiology, Drexel University College of Medicine; Philadelphia, PennsylvaniaQin Liu - Prostate Cancer Discovery and Development Program, and Molecular and Cellular Oncogenesis Program, The Wistar Institute Cancer Center, Philadelphia, PennsylvaniaJaved Siddiqui - Michigan Center for Translational Pathology, Ann Arbor, MichiganAlessandro Fatatis - Kimmel Cancer Center, Thomas Jefferson University; Philadelphia, PennsylvaniaLucia R Languino - Prostate Cancer Discovery and Development Program, Department of Cancer Biology, Philadelphia, Pennsylvania
- Publication Details
- Cancer research (Chicago, Ill.), v 73(10), pp 3155-3167
- Publisher
- American Association for Cancer Research (AACR)
- Grant note
- R01 CA109874 || CA / National Cancer Institute : NCI R01 CA089720 || CA / National Cancer Institute : NCI P01 CA140043 || CA / National Cancer Institute : NCI
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000318903700023
- Scopus ID
- 2-s2.0-84877850441
- Other Identifier
- 991014877706804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Oncology