Molecular mechanism of skin cancer development by functional ambiguity of aPKC lamda

• Project/Area Number: 17K10227
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Akita University
• Principal Investigator: Manabe Motomu 秋田大学, 医学系研究科, 名誉教授 (30138309)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 細胞極性 / aPKC / プロテインキナーゼC / 有棘細胞癌 / シグナル伝達 / 化学発癌 / 創傷治癒 / 皮膚癌 / 皮膚悪性腫瘍

Outline of Final Research Achievements

Atypical protein kinase Cλ (aPKCλ), a member of the protein kinase C family, regulates cell polarity. Two-step chemical carcinogenesis experiments in epidermis-specific aPKCλ-deficient mice revealed that aPKCλ can act positively or negatively on the development of squamous cell carcinoma, depending on the genetic background. On the other hand, in wound healing experiments, we have found that epidermis-specific aPKCλ-deficient mice showed delayed wound healing compared to control mice, and that aPKCλ regulates the direction of epidermal cell migration during wound healing.

Academic Significance and Societal Importance of the Research Achievements

有棘細胞癌は年齢ともに増加する傾向があり、今後超高齢化社会を迎えるわが国では、有棘細胞癌患者がますます増加することが予想される。有棘細胞癌は表皮の細胞の極性の乱れを特徴とし、また創傷治癒過程の異常により有棘細胞癌が発生することも知られている。本研究では、細胞極性制御因子aPKCλが、創傷治癒過程と有棘細胞癌の発症の双方において重要な役割を果たす分子であることを明らかにした。今後、aPKCλの活性を制御することによって、創傷治癒を促進し、有棘細胞癌の発症を抑えることが可能になると考えられる。

Research Products

• [Journal Article] Sox13 is a novel early marker for hair follicle development. (2019)
  • Author(s): Noto M, Noguchi N, Ishimura A, Kiyonari H, Abe T, Suzuki T, Hasunuma N, Taira M, Manabe M, Osada SI.
  • Journal Title: Biochem Biophys Res Commun Volume: 509 Issue: 4 Pages: 862-868
  • DOI: 10.1016/j.bbrc.2018.12.163
  • Peer Reviewed
• [Journal Article] Atypical protein kinase C isoforms differentially regulate directional keratinocyte migration during wound healing (2019)
  • Author(s): Noguchi N, Hirose T, Suzuki T, Kagaya M, Chida K, Ohno S, Manabe M, Osada S
  • Journal Title: J Dermatol Sci Volume: 93 Issue: 2 Pages: 101-108
  • DOI: 10.1016/j.jdermsci.2019.01.001
  • Peer Reviewed
• [Journal Article] Incidence rate of cutaneous squamous cell carcinoma is rapidly increasing in Akita Prefecture: Urgent alert for super-aged society (2019)
  • Author(s): Umezono Y, Sato Y, Noto M, Yamada K, Noguchi N, Hasunuma N, Osada SI, Manabe M
  • Journal Title: J Dermatol Volume: 46 Issue: 3 Pages: 259-262
  • DOI: 10.1111/1346-8138.14759
  • Peer Reviewed
• [Journal Article] The cost burden of psoriasis treated with biologics in Akita prefecture (2018)
  • Author(s): Mizusawa Y, Yamakawa T, Yamada K, Hasunuma N, Osada SI, Manabe M.
  • Journal Title: Akita J Med Volume: 45 Pages: 99-103
  • NAID: 40021943273
• [Journal Article] Skin grafting cases by negative pressure wound therapy for the treatment of skin tumors and intractable cutaneous ulcers (2018)
  • Author(s): Tomura Y, Noto M, Yamada K, Hasunuma N, Osada SI, Manabe M
  • Journal Title: Akita J Med Volume: 45 Pages: 105-111
  • NAID: 40021943294
• [Journal Article] Topical 3-bromopyruvate is a novel targeted therapy for melanoma in a preclinical model (2018)
  • Author(s): Yamada M, Kagaya M, Noguchi N, Ueki S, Hasunuma N, Osada SI, Manabe M.
  • Journal Title: J Dermatol Sci Volume: 92 Issue: 2 Pages: 134-142
  • DOI: 10.1016/j.jdermsci.2018.08.009
  • Peer Reviewed
• [Presentation] Sox13 is a novel marker for hair follicle development and differentiation (2019)
  • Author(s): Noto M，Noguchi N，Manabe M，Osada SI
  • Organizer: 49th Annunal European Society for Dermatological Research Meeting
  • Int'l Joint Research
• [Presentation] Topical 3-bromopyruvate is a novel targeted therapy for melanoma in preclinical model． (2019)
  • Author(s): Yamada M，Kagaya M，Noguchi N，Osada SI，Manabe M
  • Organizer: 日本研究皮膚科学会第44回年次学術大会
• [Presentation] 師の背中を追って：皮膚バリア研究からの長い旅路 (2019)
  • Author(s): 眞鍋 求
  • Organizer: 日皮会東北六県合同地方会学術大会第386回例会（眞鍋 求教授 退官記念大会）
  • Invited
• [Presentation] 皮膚バリア研究の自分史：師の背中を追って (2019)
  • Author(s): 眞鍋 求
  • Organizer: 第34回角化症研究会
  • Invited
• [Presentation] Differential rules of atypical protein kinase C isoforms in wound healing (2017)
  • Author(s): Shin-Ichi Osada，Natsuko Noguchi，Tomonori Hirose，Tomoko Suzuki，Masami Kagaya，Kazuhiro Chida，Shigeo Ohno and Motomu Manabe
  • Organizer: 47th Annual European Society for Dermatological Research
• [Presentation] A cell polarity protein，aPKCλ，regulates hair follicle regeneration after wounding． (2017)
  • Author(s): Shin-Ichi Osada，Natsuko Noguchi，Tomonori Hirose，Tomoko Suzuki，Masami Kagaya，Kazuhiro Chida，Shigeo Ohno and Motomu Manabe
  • Organizer: 10th World Congress for Hair Research
• [Presentation] Atypical protein kinase C isoform，aPKCλ，regulates directional cell migration during wound healing (2017)
  • Author(s): Shin-Ichi Osada，Natsuko Noguchi，Tomonori Hirose，Tomoko Suzuki，Masami Kagaya，Kazuhiro Chida，Shigeo Ohno and Motomu Manabe
  • Organizer: 日本研究皮膚科学会第42回年次学術大会・総会
• [Presentation] Differential Regulation of wound healing by atypical protein kinase C isoforms． (2017)
  • Author(s): Natsuko Noguchi，Shin-Ichi Osada，Tomonori Hirose，Tomoko Suzuki，Masami Kagaya，Kazuhiro Chida，Shigeo Ohno and Motomu Manabe
  • Organizer: 第31回表皮細胞研究会