Protein 4.1B suppresses prostate cancer progression and metastasis.

TitleProtein 4.1B suppresses prostate cancer progression and metastasis.
Publication TypeJournal Article
Year of Publication2007
AuthorsWong, SY, Haack, H, Kissil, JL, Barry, M, Bronson, RT, Shen, SS, Whittaker, CA, Crowley, D, Hynes, RO
JournalProc Natl Acad Sci U S A
Date Published2007 Jul 31
KeywordsAdenocarcinoma, 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

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.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID17640904
PubMed Central IDPMC1924789
Grant ListR01 CA 17007 / CA / NCI NIH HHS / United States
U54 CA 112967 / CA / NCI NIH HHS / United States