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Ohki, Rieko; Saito, Kozue; Chen, Yu; Kawase, Tatsuya; Hiraoka, Nobuyoshi; Saigawa, Raira; Minegishi, Maiko; Aita, Yukie; Yanai, Goichi; Shimizu, Hiroko; Yachida, Shinichi; Sakata, Naoaki; Doi, Ryuichiro; Kosuge, Tomoo; Shimada, Kazuaki; Tycko, Benjamin; Tsukada, Toshihiko; Kanai, Yae; Sumi, Shoichiro; Namiki, Hideo; Taya, Yoichi; Shibata, Tatsuhiro; Nakagama, Hitoshi

PHLDA3 is a novel tumor suppressor of pancreatic neuroendocrine tumors

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  • Media type: E-Article
  • Title: PHLDA3 is a novel tumor suppressor of pancreatic neuroendocrine tumors
  • Contributor: Ohki, Rieko; Saito, Kozue; Chen, Yu; Kawase, Tatsuya; Hiraoka, Nobuyoshi; Saigawa, Raira; Minegishi, Maiko; Aita, Yukie; Yanai, Goichi; Shimizu, Hiroko; Yachida, Shinichi; Sakata, Naoaki; Doi, Ryuichiro; Kosuge, Tomoo; Shimada, Kazuaki; Tycko, Benjamin; Tsukada, Toshihiko; Kanai, Yae; Sumi, Shoichiro; Namiki, Hideo; Taya, Yoichi; Shibata, Tatsuhiro; Nakagama, Hitoshi
  • Published: Proceedings of the National Academy of Sciences, 2014
  • Published in: Proceedings of the National Academy of Sciences, 111 (2014) 23
  • Language: English
  • DOI: 10.1073/pnas.1319962111
  • ISSN: 0027-8424; 1091-6490
  • Origination:
  • Footnote:
  • Description: Significance Pancreatic neuroendocrine tumors (PanNETs) are a rare pathology, and molecular mechanisms underlying their development have not been well defined. This article shows that a two-hit inactivation of the PHLDA3 gene is required for PanNET development: methylation of the locus and loss of heterozygosity. PHLDA3 functions as a suppressor of PanNETs via repression of Akt activity and downstream Akt-regulated biological processes. In addition, the tumor-suppressing pathway mediated by MEN1, a well known suppressor of PanNETs, is dependent on the pathway mediated by PHLDA3, and inactivation of PHLDA3 and MEN1 cooperatively contribute to PanNET development. A novel PHLDA3-mediated pathway of tumor suppression that is important in the development of PanNETs is demonstrated, and the findings may contribute to personalized medicine of PanNET patients.
  • Access State: Open Access