Protein 4.1B suppresses prostate cancer progression and metastasis.
Document Type
Article
Publication Date
2007
Keywords
Animals, Cell-Differentiation, Cell-Line-Tumor, Disease-Progression, Down-Regulation, Humans, Male, Membrane-Proteins, Mice, Mice-Inbred-C57BL, Mice-Knockout, Neoplasm-Metastasis, Prostatic-Neoplasms, Tumor-Suppressor-Proteins, Xenograft-Model-Antitumor-Assays
First Page
12784
Last Page
12789
JAX Source
Proc Natl Acad Sci U S A 2007 Jul; 104(31):12784-9.
Abstract
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 4.1B 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.
Recommended Citation
Wong SY,
Haack H,
Kissil JL,
Barry M,
Bronson RT,
Shen SS,
Whittaker CA,
Crowley D,
Hynes RO.
Protein 4.1B suppresses prostate cancer progression and metastasis. Proc Natl Acad Sci U S A 2007 Jul; 104(31):12784-9.