Title

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

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.