Title | Protein 4.1B suppresses prostate cancer progression and metastasis. |
Publication Type | Journal Article |
Year of Publication | 2007 |
Authors | Wong, SY, Haack, H, Kissil, JL, Barry, M, Bronson, RT, Shen, SS, Whittaker, CA, Crowley, D, Hynes, RO |
Journal | Proc Natl Acad Sci U S A |
Volume | 104 |
Issue | 31 |
Pagination | 12784-9 |
Date Published | 2007 Jul 31 |
ISSN | 0027-8424 |
Keywords | Adenocarcinoma, Animals, Cell Differentiation, Cell Line, Tumor, Disease Progression, Down-Regulation, Humans, Male, Membrane Proteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Microfilament Proteins, Neoplasm Metastasis, Prostatic Neoplasms, Tumor Suppressor Proteins, Xenograft Model Antitumor Assays |
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. |
DOI | 10.1073/pnas.0705499104 |
Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
PubMed ID | 17640904 |
PubMed Central ID | PMC1924789 |
Grant List | R01 CA 17007 / CA / NCI NIH HHS / United States U54 CA 112967 / CA / NCI NIH HHS / United States |