Protein 4.1B suppresses prostate cancer progression and metastasis. Wong SY, Haack H, Kissil JL*, Barry M, Bronson RT, Shen SS, Whittaker CA, Crowley D, Hynes RO, Howard Hughes Medical Institute, Massachusetts Institute of Technology Center for Cancer Research, Cambridge, MA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA; *Molecular and Cellular Oncogenesis Program...

Full title. Protein 4.1B suppresses prostate cancer progression and metastasis. Wong SY, Haack H, Kissil JL*, Barry M, Bronson RT, Shen SS, Whittaker CA, Crowley D, Hynes RO, Howard Hughes Medical Institute, Massachusetts Institute of Technology Center for Cancer Research, Cambridge, MA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA; *Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA; Department of Biomedical Sciences, Tufts School of Veterinary Medicine, North Grafton, MA. 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.