title: Protein 4.1B suppresses prostate cancer progression and metastasis.
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.
authors.affiliation: Howard Hughes Medical Institute, Massachusetts Institute of Technology Center for Cancer Research, Cambridge, MA 02139, USA.
authors.forename: Sunny Y
authors.initials: SY
authors.lastname: Wong
authors.forename: Herbert
authors.initials: H
authors.lastname: Haack
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Kissil
authors.forename: Marc
authors.initials: M
authors.lastname: Barry
authors.forename: Roderick T
authors.initials: RT
authors.lastname: Bronson
authors.forename: Steven S
authors.initials: SS
authors.lastname: Shen
authors.forename: Charles A
authors.initials: CA
authors.lastname: Whittaker
authors.forename: Denise
authors.initials: D
authors.lastname: Crowley
authors.forename: Richard O
authors.initials: RO
authors.lastname: Hynes
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D018450:Disease Progression; D015536:Down-Regulation; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: C116887:EPB41L3 protein, human; C488402:Epb41l3 protein, mouse; D008565:Membrane Proteins; D008840:Microfilament Proteins; D025521:Tumor Suppressor Proteins