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- Title
Ribophorin II regulates breast tumor initiation and metastasis through the functional suppression of GSK3β.
- Authors
Ryou-u Takahashi; Fumitaka Takeshita; Kimi Honma; Masaya Ono; Kikuya Kato; Takahiro Ochiya
- Abstract
Mutant p53 (mtp53) gain of function (GOF) contributes to various aspects of tumor progression including cancer stem cell (CSC) property acquisition.Akey factor ofGOFis stabilization and accumulation of mtp53. However, the precise molecular mechanism of the mtp53 oncogenic activity remains unclear. Here, we show that ribophorin II (RPN2) regulates CSC properties through the stabilization of mtp53 (R280K and del126-133) in breast cancer. RPN2 stabilized mtp53 by inactivation of glycogen synthase kinase-3β (GSK3β) which suppresses Snail, a master regulator of epithelial to mesenchymal transition. RPN2 knockdown promoted GSK3β-mediated suppression of heat shock proteins that are essential for mtp53 stabilization. Furthermore, our study reveals that high expression of RPN2 and concomitant accumulation of mtp53 were associated with cancer tissues in a small cohort of metastatic breast cancer patients. These findings elucidate a molecular mechanism for mtp53 stabilization and suggest that RPN2 could be a promising target for anti-CSC therapy
- Subjects
CANCER invasiveness; HEAT shock proteins; HEALTH care rationing; STEM cells; RIBOPHORINS
- Publication
Scientific Reports, 2013, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep02474