Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 31, Pages 12784-12789Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0705499104
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- NCI NIH HHS [U54 CA 112967, R01 CA017007, U54 CA112967, R01 CA 17007] Funding Source: Medline
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Protein 4.1B is a 4.1/ezrin/radixin/moesin domain-containing protein whose expression is frequently lost in a variety of human tumors, including meningiomas, non-small-cell lung cancers, and breast carcinomas. However, its potential tumor-suppressive function under in vivo conditions remains to be validated. In a screen for genes involved with prostate cancer metastasis, we found that 4.1B expression is reduced in highly metastatic tumors. Down-regulation of 4.1B increased the metastatic propensity of poorly metastatic cells in an orthotopic model of prostate cancer. Furthermore, 4.1B-deficient mice displayed increased susceptibility for developing aggressive, spontaneous prostate carcinomas. In both cases, enhanced tumor malignancy was associated with reduced apoptosis. Because expression of Protein 4.1 B is frequently down-regulated in human clinical prostate cancer, as well as in a spectrum of other tumor types, these results suggest a more general role for Protein 4.1B as a negative regulator of cancer progression to metastatic disease.
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