期刊
MOLECULAR ONCOLOGY
卷 15, 期 7, 页码 1956-1969出版社
WILEY
DOI: 10.1002/1878-0261.12922
关键词
cell adhesion; CHD1; ERG; junction plakoglobin; prostate cancer; WNT signaling
类别
资金
- German Research Foundation [LA3373/2-3, LA3373/8-1]
- Ministry of Science and Innovation [SAF2017-84092-R]
- Severo Ochoa Excellence [SEV-2016-0644]
- Departments of Industry, Tourism and Trade
- Innovation Technology of the Government of the Autonomous Community of the Basque Country
- ProjektDEAL
The junction plakoglobin (JUP) protein has both oncogenic and tumor suppressor functions in prostate cancer, with high expression associated with adverse tumor characteristics and poor prognosis in some patient subsets.
Both oncogenic and tumor suppressor functions have been described for junction plakoglobin (JUP), also known as gamma-catenin. To clarify the role of JUP in prostate cancer, JUP protein expression was immunohistochemically detected in a tissue microarray containing 11 267 individual prostatectomy specimens. Considering all patients, high JUP expression was associated with adverse tumor stage (P = 0.0002), high Gleason grade (P < 0.0001), and lymph node metastases (P = 0.011). These associations were driven mainly by the subset without TMPRSS2:ERG fusion, in which high JUP expression was an independent predictor of poor prognosis (multivariate analyses, P = 0.0054) and early biochemical recurrence (P = 0.0003). High JUP expression was further linked to strong androgen receptor expression (P < 0.0001), high cell proliferation, and PTEN and FOXP1 deletion (P < 0.0001). In the ERG-negative subset, high JUP expression was additionally linked to MAP3K7 (P = 0.0007) and CHD1 deletion (P = 0.0021). Contrasting the overall prognostic effect of JUP, low JUP expression indicated poor prognosis in the fraction of CHD1-deleted patients (P = 0.039). In this subset, the association of high JUP and high cell proliferation was specifically absent. In conclusion, the controversial biological roles of JUP are reflected by antagonistic prognostic effects in distinct prostate cancer patient subsets.
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