Protein 4.1B suppresses prostate cancer progression and metastasis.
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.
Wong
Sunny Y
SY
Howard Hughes Medical Institute, Massachusetts Institute of Technology Center for Cancer Research, Cambridge, MA 02139, USA.
Haack
Herbert
H
Kissil
Joseph L
JL
Barry
Marc
M
Bronson
Roderick T
RT
Shen
Steven S
SS
Whittaker
Charles A
CA
Crowley
Denise
D
Hynes
Richard O
RO
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
C116887:EPB41L3 protein, human; C488402:Epb41l3 protein, mouse; D008565:Membrane Proteins; D008840:Microfilament Proteins; D025521:Tumor Suppressor Proteins