The NF-κB subunit RelB regulates the migration and invasion abilities and the radio-sensitivity of prostate cancer cells.
NF-κB subunits play important roles in carcinogenesis of a variety of human malignancies and response to cancer therapy; however, the contribution of an individual subunit has not been thoroughly defined. Constitutive activation of the canonical NF-κB subunit is a critical event in prostate carcinogenesis. Recent findings point out that RelB, which contributes to the non-canonical NF-κB activity, functions importantly in the prostate cancer progression. Here, we investigated systemically the functional roles of RelB in prostate cancer and examine its significance as a therapeutic target. Targeting RelB using short hairpin RNA approach in androgen-independent DU145 prostate cancer cells interfered with various biological behaviors of cells. We observed that RelB knockdown inhibited prostate cancer cell growth, migration, and invasion, and enhanced proteasome inhibitor sensitivity. The altered expression of anti-apoptotic gene Bcl-2 played critical roles in regulating both spontaneous and radiation-induced apoptosis in the presence of RelB knockdown. For the first time, we showed that RelB knockdown significantly attenuated the migration and invasion of DU145 prostate cancer cells, due to the reduction of integrin β-1. Collectively, we provided evidence that RelB functioned as an oncogene in prostate cancer. Developing a RelB-targeted therapeutic intervention, is valuable in treating advanced, metastatic prostate cancer.
Central Lab, The First Affiliated Hospital of Soochow University Suzhou, Jiangsu 215006, P.R. China.
Jie
J
Wang
Department of Oncology, The First People's Hospital of Yancheng, Yancheng, Jiangsu 224000, P.R. China.
Suqin
S
Yi
Central Lab, The First Affiliated Hospital of Soochow University Suzhou, Jiangsu 215006, P.R. China.
Jun
J
Zhou
Central Lab, The First Affiliated Hospital of Soochow University Suzhou, Jiangsu 215006, P.R. China.
Youtao
Y
Zhang
Central Lab, The First Affiliated Hospital of Soochow University Suzhou, Jiangsu 215006, P.R. China.
Feng
F
Guo
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D019012:Integrin beta1 / Q000096:biosynthesis*; D008297:Male; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D061988:Proteasome Inhibitors / Q000008:administration & dosage; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D051841:Transcription Factor RelB / Q000096:biosynthesis / Q000235:genetics*
D019012:Integrin beta1; D061988:Proteasome Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; C497593:RELB protein, human; D034741:RNA, Small Interfering; D051841:Transcription Factor RelB