Ppp6c-deficiency and cancer predisposition

• Project/Area Number: 15K20237
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Miyagi Prefectural Hospital Organization Miyagi Cancer Center
• Principal Investigator: MOMOI Yuki 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 共同研究員 (10750440)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 口腔咽頭科学

Outline of Final Research Achievements

Several experiment using biochemical experiments have suggested that protein phosphatase 6 (PP6) functions at cell cycle check point, suppresses NFkB signaling, and also functions in DNA repair. However, whether PP6 is involved in carcinogenesis has not been examined. We previously reported that deficiency in the gene encoding the catalytic subunit of protein phosphatase 6 (Ppp6c) predisposes mouse skin tissue to papilloma formation initiated by DMBA. Then, we demonstrated that Ppp6c loss acts as a tumor promoter in UVB-induced basal cell carcinogenesis. Importantly, somatic mutations in Ppp6c gene have been identified in approximately 10% of malignant melanoma patients harboring Braf or Nras mutations. In this experiment, we found that induction of double mutation (Ppp6c deficiency and KrasG12D expression) in the cytokeratin 14 positive cells drives cell proliferation, and leaded to hyperplasia of squamous epithelium tissue.

Research Products

• [Journal Article] The protein phosphatase 6 catalytic subunit (Ppp6c) is indispensable for proper post-implantation embryogenesis. (2016)
  • Author(s): Ogoh, H., Tanuma, N., Matsui, Y., Hayakawa, N., Inagaki, A., Sumiyoshi, M., Momoi, Y., Kishimoto, A., Suzuki, M., Sasaki, N., Ohuchi, T., Nomura, M., Teruya, Y., Yasuda, K., Watanabe, T., Shima, H.
  • Journal Title: Mechanisms of Development Volume: 139 Pages: 1-9
  • DOI: 10.1016/j.mod.2016.02.001
  • Peer Reviewed / Open Access
• [Journal Article] Abrogation of protein phosphatase 6 promotes skin carcinogenesis induced by DMBA (2015)
  • Author(s): Hayashi K, Momoi Y , Tanuma N, Kishimoto A, Ogoh H, Kato H, Suzuki M, Sakamoto Y, Inoue Y, Nomura M, Kiyonari H, Sakayori M, Fukamachi K, Kakugawa Y, Yamashita Y, Ito S, Sato I, Suzuki A, Nishio M, Suganuma M, Watanabe T, and Shima H
  • Journal Title: Oncogene Volume: 印刷中 Issue: 35 Pages: 4647-55
  • DOI: 10.1038/onc.2014.398
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Loss of protein phosphatase 6 in mouse keratinocytes increases susceptibility to ultraviolet-B-induced carcinogenesis. (2015)
  • Author(s): Kato H, Kurosawa K, Inoue Y, Tanuma N, Momoi Y, Hayashi K, Ogoh H, Nomura M, Sakayori M, Kakugawa Y, Yamashita Y, Miura K, Maemondo M, Katakura R, Ito S, Sato M, Sato I, Chiba N, Watanabe T, Shima H.
  • Journal Title: Cancer Lett. Volume: 365 Issue: 2 Pages: 223-228
  • DOI: 10.1016/j.canlet.2015.05.022
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 発がんプロモーターオカダ酸の標的、PP6の皮膚がん抑制遺伝子としての意義 (2016)
  • Author(s): 島礼、黒沢是之、小河穂波、桃井勇貴、井上維、田沼延公、渡邊利雄
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 宮城県・仙台市
  • Year and Date: 2016-09-25
• [Presentation] 脱リン酸化酵素PP6は、皮膚がん抑制遺伝子である (2016)
  • Author(s): 黒沢是之、桃井勇貴、井上唯、小河穂波、後藤孝浩、田沼延公、渡邊利雄、島礼
  • Organizer: 第７回 プロテインホスファターゼ研究会学術集会
  • Place of Presentation: 自然科学研究機構（愛知県、岡崎市）
  • Year and Date: 2016-01-29