MP33-04 HMGB1 PROMOTES TUMOR PROGRESSION AND INVASION THROUGH HMGB1/TNFR1/NF-ΚB AXIS IN CASTRATION-RESISTANT PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I (MP33)1 Sep 2021MP33-04 HMGB1 PROMOTES TUMOR PROGRESSION AND INVASION THROUGH HMGB1/TNFR1/NF-ΚB AXIS IN CASTRATION-RESISTANT PROSTATE CANCER Ae Ryang Jung, Yong Hyun Park, Dong Ho Shin, Hyong Woo Moon, U-Syn Ha, Sung-Hoo Hong, Ji Youl Lee, and Sae Woong Kim JungAe Jung More articles by this author , ParkYong Park ShinDong Shin MoonHyong Moon HaU-Syn Ha HongSung-Hoo Hong LeeJi Lee KimSae View All Author Informationhttps://doi.org/10.1097/JU.0000000000002042.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION OBJECTIVE: Prostate cancer (PCa) is the most common male cancer. Most patients treated with androgen deprivation therapy progress castration-resistant PCa. To overcome limitations current treatment, identification more effective treatment targets urgently needed. High mobility group box 1 protein (HMGB1) known be associated progression, metastasis, poor prognosis several solid tumors; however, role in PCa remains unclear. Thus, we aimed evaluate clinical significance biological mechanism METHODS: After transient transfection PC3 DU-145 cells siRNA, diverse experiments were performed changes proliferation, apoptosis, invasion. We subsequently investigated whether downregulation could affect NF-κB signaling using a human proteome profiler array. identify TNFR responsible for binding, Co-IP assay on HEK293 following co-transfection FLAG-HMGB1 HA-TNFR1, 3, or 5. Finally, determined impact overall survival Cancer Genome Atlas (TCGA) datasets. further validated prognostic importance immunofluorescence staining 131 from Korean Bank. RESULTS: The inhibition expression significantly reduced cell invasive capacity, pathway vitro. Our results showed that critical factor development progression Moreover, found directly interacts TNFR1, TNFR1 overexpression knockdown reversed effects knockdown. In TCGA data set (n=498), was altered 61 498 (12%). Overall shorter high (medians: 115.0 months vs. not reached; p=0.0296). Bank cohort, positive areas differed BPH, low-, intermediate-, high-risk, metastatic (4.6, 11.9, 18.6, 19.7, 23.4%, p<0.001). During median follow-up 32 months, increased significant decrease biochemical recurrence free Kaplan-Meier analysis. CONCLUSIONS: suggest binding promotes tumor activating PCa, HMGB1/TNFR1/NF-κB serve as novel therapeutic target improving therapy. Source Funding: None © 2021 American Urological Association Education Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e607-e607 Advertisement Copyright Permissions© Inc.MetricsAuthor Information Expand Loading ...