MP01-01 TNFAIP2: A POTENTIAL TARGET IN PLATINUM RESISTANCE UROTHELIAL CARCINOMA

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You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I (MP01)1 Apr 2020MP01-01 TNFAIP2: A POTENTIAL TARGET IN PLATINUM RESISTANCE UROTHELIAL CARCINOMA Naoya Niwa*, Nobuyuki Tanaka, Hiroshi Hongo, Yasumasa Miyazaki, Kimiharu Takamatsu, Yota Yasumizu, Toshikazu Takeda, Kazuhiro Matsumoto, Shinya Morita, Takeo Kosaka, Ryuichi Mizuno, Eiji Kikuchi, Hiroshi Asanuma, Shuji Mikami, and Mototsugu Oya Naoya Niwa*Naoya Niwa* More articles by this author , Nobuyuki TanakaNobuyuki Tanaka More articles by this author , Hiroshi HongoHiroshi Hongo More articles by this author , Yasumasa MiyazakiYasumasa Miyazaki More articles by this author , Kimiharu TakamatsuKimiharu Takamatsu More articles by this author , Yota YasumizuYota Yasumizu More articles by this author , Toshikazu TakedaToshikazu Takeda More articles by this author , Kazuhiro MatsumotoKazuhiro Matsumoto More articles by this author , Shinya MoritaShinya Morita More articles by this author , Takeo KosakaTakeo Kosaka More articles by this author , Ryuichi MizunoRyuichi Mizuno More articles by this author , Eiji KikuchiEiji Kikuchi More articles by this author , Hiroshi AsanumaHiroshi Asanuma More articles by this author , Shuji MikamiShuji Mikami More articles by this author , and Mototsugu OyaMototsugu Oya More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000815.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cisplatin (CDDP)-based chemotherapy is the gold standard treatment for patients with locally advanced or metastatic urothelial carcinoma (UC). However, the phenotypic hallmark of tumors often changes after CDDP, with the acquisition of epithelial-to-mesenchymal transition (EMT) and platinum resistance. Furthermore, the mechanisms by which cancer cells acquire EMT under the control of CDDP remain unclear. Following an investigation of urothelial carcinoma before and after the acquisition of platinum resistance, we offered the new target TNF alpha induced protein 2 (TNFAIP2), which led to EMT and tumor invasion in acquired platinum-resistance UC cells. METHODS: TNFAIP2 expression in cancers was examined at the protein and transcription levels. We investigated the relationship between TNFAIP2 and oncological outcomes in UC patients, and the relationship between TNFAIP2 and EMT in vitro. Furthermore, A potential target for TNFAIP2 during EMT was assessed by microarray. RESULTS: Clinically, up-regulated TNFAIP2 expression was identified as a significant predictor of mortality following surgery in three different cohorts of patients with UC (n = 156, n = 119, and n = 54). The knockdown of TNFAIP2 resulted in up-regulated E-cadherin expression and down-regulated TWIST1 expression, which decreased motile function in acquired platinum-resistance UC cells. TNFAIP2 overexpression led to down-regulated E-cadherin expression and up-regulated TWIST1 expression in platinum-naïve UC cells. Clinical investigations on matched pre- and post-CDDP-treated UC sections confirmed up-regulated TNFAIP2 expression in CDDP-treated tumors, but down-regulated E-cadherin expression. A global gene expression analysis following TNFAIP2 knockdown identified MTDH as a positive regulator of TNFAIP2-derived EMT acquisition in cancer cells. CONCLUSIONS: he present results suggest a relationship between TNFAIP2 and EMT in UC under the control of CDDP, in which MTDH expression levels in UC cells are vital for promoting TNFAIP2-derived EMT acquisition. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1-e1 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Naoya Niwa* More articles by this author Nobuyuki Tanaka More articles by this author Hiroshi Hongo More articles by this author Yasumasa Miyazaki More articles by this author Kimiharu Takamatsu More articles by this author Yota Yasumizu More articles by this author Toshikazu Takeda More articles by this author Kazuhiro Matsumoto More articles by this author Shinya Morita More articles by this author Takeo Kosaka More articles by this author Ryuichi Mizuno More articles by this author Eiji Kikuchi More articles by this author Hiroshi Asanuma More articles by this author Shuji Mikami More articles by this author Mototsugu Oya More articles by this author Expand All Advertisement PDF downloadLoading ...