Inhibition of nestin phosphorylation in pancreatic cancer cells

• Project/Area Number: 25462127
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: Matsuda Yoko 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (20363187)
• Co-Investigator(Kenkyū-buntansha): Matsushita Akira 日本医科大学, 医学部, 助教 (70449263) ; Shinji Seiichi 日本医科大学, 医学部, 助教 (80409193) ; Ishiwata Toshiyuki 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (90203041)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 膵癌 / nestin / 幹細胞 / 細胞骨格 / リン酸化 / 浸潤 / 転移 / 増殖 / 遊走

Outline of Final Research Achievements

In this study, we examined the roles of phosphorylated nestin in pancreatic cancer cells. We found nestin phosphorylation in mitotic phase of human pancreatic cancer cells. Nestin phosphorylation was correlated with MIB-1 index in human pancreatic cancer tissues. Transfection of pancreatic cancer cells with nestin mutated at one phosphorylation site inhibited cell growth. Transfecting cells with wild-type nestin or with nestin mutated at one site increased migration and invasion. In addition, transfection with nestin mutated at two phosphorylation sites inhibited migration, invasion, and liver metastases. Nestin phosphorylation at these two sites was decreased upon treatment with inhibitors for cyclin dependent kinases, AKT, and Aurora. Inhibiting nestin phosphorylation at these two sites may represent a novel therapeutic strategy for pancreatic cancer.

Research Products

• [Journal Article] Clinicopathological features of 15 occult and 178 clinical pancreatic ductal adenocarcinomas in 8339 autopsied elderly patients. (2016)
  • Author(s): 1.Matsuda Y, Ishiwata T, Yachida S, Suzuki A, Hamashima Y, Hamayasu H, Yoshimura H, Honma N, Aida J, Takubo K, Arai T.
  • Journal Title: Pancreas Volume: 45 Issue: 2 Pages: 234-40
  • DOI: 10.1097/mpa.0000000000000447
  • Peer Reviewed
• [Journal Article] Mitotic index and multipolar mitosis in routine histologic sections as prognostic markers of pancreatic cancers: A clinicopathological study. (2016)
  • Author(s): 2.Matsuda Y, Yoshimura H, Ishiwata T, Sumiyoshi H, Matsushita A, Nakamura Y, Aida J, Uchida E, Takubo K, Arai T.
  • Journal Title: Pancreatology Volume: 16 Issue: 1 Pages: 127-32
  • DOI: 10.1016/j.pan.2015.10.005
  • Peer Reviewed
• [Journal Article] Ａｄｍｉｎｉｓｔｒａｔｉｏｎ ｏｆ ｓｍａｌｌ ｉｎｔｅｒｆｅｒｉｎｇ ＲＮＡ ｔａｒｇｅｔｉｎｇ ｈｕｍａｎ ｎｅｓｔｉｎ ｉｎｈｉｂｉｔｓ ｐａｎｃｒｅａｔｉｃ ｃａｎｃｅｒ ｃｅｌｌ ｐｒｏｌｉｆｅｒａｔｉｏｎ ａｎｄ ｍｅｔａｓｔａｓｉｓ． (2016)
  • Author(s): Ｍａｔｓｕｄａ Ｙ, Ishiwata T, Yoshimura H, Yamashita S, Ushijima T, Arai T.
  • Journal Title: Ｐａｎｃｒｅａｓ Volume: ４５ Issue: 1 Pages: 93-100
  • DOI: 10.1097/mpa.0000000000000427
  • Peer Reviewed
• [Journal Article] Nestin regulates proliferation, migration, invasion and stemness of lung adenocarcinoma (2014)
  • Author(s): Narita K, Matsuda Y, Seike M, Naito Z, Gemma A, Ishiwata T
  • Journal Title: Int J Oncol Volume: 44(4) Issue: 4 Pages: 1118-30
  • DOI: 10.3892/ijo.2014.2278
  • Peer Reviewed
• [Journal Article] Nestin delineates pancreatic cancer stem cells in metastatic foci of NOD/Shi-scid IL2Rγ(null) (NOG) mice (2014)
  • Author(s): Matsuda Y, Yoshimura H, Ueda J, Naito Z, Korc M, Ishiwata T
  • Journal Title: Am J Pathol Volume: 184(3) Issue: 3 Pages: 674-85
  • DOI: 10.1016/j.ajpath.2013.11.014
  • Peer Reviewed
• [Journal Article] Phosphorylation of Thr(1495) of nestin in a mouse model of cerebral ischemia and reperfusion damage (2013)
  • Author(s): Matsuda Y, Suzuki G, Kusano T, Kawamoto Y, Yoshimura H, Fuse A, Yokota H, Naito Zand Ishiwata T
  • Journal Title: Ｐａｔｈｏｌｏｇｙ Ｉｎｔｅｒｎａｔｉｏｎａｌ Volume: 63 Issue: 9 Pages: 448-56
  • DOI: 10.1111/pin.12092
  • Peer Reviewed
• [Journal Article] Nestin is highly expressed in advanced-stage melanomas and neurotized nevi (2013)
  • Author(s): Akiyama M, Matsuda Y, Ishiwata T, Naito Z, Kawana S
  • Journal Title: Oncol Rep Volume: 29 Issue: 4 Pages: 1595-9
  • DOI: 10.3892/or.2013.2287
  • Peer Reviewed
• [Presentation] Telomere Shortening in the Pancreas: Relationships with Aging, Cancers and Tissue Stem Cells (2015)
  • Author(s): Matsuda Y
  • Organizer: Telomere workshop in Korea
  • Place of Presentation: ソウル、韓国
  • Year and Date: 2015-11-11
  • Int'l Joint Research / Invited
• [Presentation] Occult and clinical pancreatic cancers in elderly patients. (2015)
  • Author(s): Matsuda Y, Suzuki A, Hamashima Y, Hamayasu H, Yoshimura H, Ishiwata T, Arai T.
  • Organizer: AACR Annual Meeting 2015
  • Place of Presentation: フィラデルフィア、米国
  • Year and Date: 2015-04-18
  • Int'l Joint Research
• [Presentation] Inhibition of Phosphorylation of Nestin Decrease Pancreatic Cancer Cell Growth. (2013)
  • Author(s): Matsuda Y, Yoshimura H, Suzuki T, Naito Z, Kawahara K, 他3名
  • Organizer: American association for cancer research, 104th annual meeting
  • Place of Presentation: Washington, DC
• [Presentation] 膵癌の新たな治療標的としてのリン酸化nestin. (2013)
  • Author(s): 2. 松田 陽子, 吉村 久志, 内藤 善哉, 鈴木 妙子, 河本 陽子, 川原 清子, 石渡 俊行
  • Organizer: 第72回 日本癌学会学術総会.
  • Place of Presentation: 神奈川