キクチ　エイジ   KIKUCHI EIJI
  菊地栄次
   所属   医学部医学科 腎泌尿器外科学
   職種   主任教授
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 TNFAIP2 expression induces epithelial-to-mesenchymal transition and confers platinum resistance in urothelial cancer cells.
掲載誌名 正式名：Laboratory investigation; a journal of technical methods and pathology
略　 称：Lab Invest
ISSNコード：1530030700236837
掲載区分国外
巻・号・頁 99(11),1702-1713頁
著者・共著者 Niwa Naoya, Tanaka Nobuyuki, Hongo Hiroshi, Miyazaki Yasumasa, Takamatsu Kimiharu, Mizuno Ryuichi, Kikuchi Eiji, Mikami Shuji, Kosaka Takeo, Oya Mototsugu
発行年月 2019/11
概要 Cisplatin (CDDP)-based chemotherapy is the gold standard treatment for many types of cancer. However, the phenotypic hallmark of tumors often changes after CDDP treatment, 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 (UC) before and after the acquisition of platinum resistance, we offer the new target TNFAIP2, which led to EMT and tumor invasion in platinum-treated UC cells. TNFAIP2 expression in cancer was examined at the protein and transcriptional levels. A potential target for TNFAIP2 during EMT was assessed by microarray. Clinically, upregulated 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). Knockdown of TNFAIP2 resulted in upregulation of E-cadherin expression and downregulation of TWIST1 expression, which decreased motile function in platinum-resistant UC cells. TNFAIP2 overexpression led to downregulation of E-cadherin expression and upregulation of TWIST1 expression in platinum-naïve UC cells. Clinical investigation of matched pre- and post-CDDP-treated UC sections confirmed upregulation of TNFAIP2 expression in CDDP-treated tumors but downregulation of E-cadherin expression. Global gene expression analysis following TNFAIP2 knockdown identified MTDH as a positive regulator of TNFAIP2-derived EMT acquisition in cancer cells. The present results suggest a relationship between TNFAIP2 and EMT in cancers under the control of CDDP, in which MTDH expression levels in cancer cells are vital for promoting TNFAIP2-derived EMT acquisition.
DOI 10.1038/s41374-019-0285-y
PMID 31263157

(c)2008 St. Marianna University School of Medicine