Numb has distinct roles in lung adenocarcinoma and squamous cell carcinomaus us

• Project/Area Number: 18K08130
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Hokkaido University
• Principal Investigator: sakakibara jun 北海道大学, 大学病院, 講師 (50374278)
• Co-Investigator(Kenkyū-buntansha): 木下 一郎 北海道大学, 大学病院, 教授 (40343008)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 肺腺癌 / 肺扁平上皮癌 / 非小細胞肺癌 / 肺癌 / 組織系 / Numb / Numbの機能

Outline of Final Research Achievements

To investigate the role of Numb in tumorigenesis of lung adenocarcinoma and squamous cell carcinoma, we firstly performed loss-of-function and gain-of-function assays. Moreover, Numb expression was investigated in surgically resected lung adenocarcinoma and squamous cell carcinoma tissues by immunohistochemistry and correlations with prognosis were analyzed. Numb suppressed the proliferation, migration, and invasion of adenocarcinoma cells. In contrast, Numb promoted the proliferation, migration, and invasion of squamous cell carcinoma cells. High Numb expression was associated with favorable prognosis in patients with lung adenocarcinoma, but not in those with squamous cell carcinoma. Collectively, our data demonstrate that Numb plays distinct roles in lung adenocarcinoma and squamous cell carcinoma. In lung adenocarcinoma, Numb impairs tumor growth, whereas in lung squamous cell carcinoma it may promote proliferation.

Academic Significance and Societal Importance of the Research Achievements

肺癌においてNumbの機能は腺癌と扁平上皮癌において違うことが示されたことからサブタイプ別に今後の治療を検討していく必要性が示された。腺癌においては腫瘍抑制的に機能しNumb高発現は予後良好であったことから腺癌においてNumbは予後予測因子となる可能性が示された。また扁平上皮癌においてはNumbは腫瘍増殖に機能しておりNumbを標的とした治療開発は今後の肺癌治療において学術的にも社会的にも意義があると考えられた。

Research Products

• [Journal Article] Bromodomain and extraterminal domain inhibition synergizes with WEE1‐inhibitor AZD1775 effect by impairing nonhomologous end joining and enhancing DNA damage in nonsmall cell lung cancer (2020)
  • Author(s): Takashima Yuta、Kikuchi Eiki、Kikuchi Junko、Suzuki Motofumi、Kikuchi Hajime、Maeda Makie、Shoji Tetsuaki、Furuta Megumi、Kinoshita Ichiro、Dosaka‐Akita Hirotoshi、Sakakibara‐Konishi Jun、Konno Satoshi
  • Journal Title: International Journal of Cancer Volume: 146 Issue: 4 Pages: 1114-1124
  • DOI: 10.1002/ijc.32515
  • NAID: 120006958367
  • Peer Reviewed
• [Journal Article] Evaluating the immunoproteasome as a potential therapeutic target in cisplatin-resistant small cell and non-small cell lung cancer (2020)
  • Author(s): Shoji T, Kikuchi E, Kikuchi J, Takashima Y, Furuta M, Takahashi H, Tsuji K, Maeda M, Kinoshita I, Dosaka-Akita H, Sakakibara-Konishi J, Konno S
  • Journal Title: Cancer Chemother Pharmacol Volume: in print Issue: 5 Pages: 843-853
  • DOI: 10.1007/s00280-020-04061-9
  • NAID: 120007032615
  • Peer Reviewed
• [Journal Article] DLL3 regulates the migration and invasion of small cell lung cancer by modulating Snail (2019)
  • Author(s): Furuta Megumi、Kikuchi Hajime、Shoji Tetsuaki、Takashima Yuta、Kikuchi Eiki、Kikuchi Junko、Kinoshita Ichiro、Dosaka‐Akita Hirotoshi、Sakakibara‐Konishi Jun
  • Journal Title: Cancer Science Volume: in print Issue: 5 Pages: 1599-1608
  • DOI: 10.1111/cas.13997
  • Peer Reviewed / Open Access
• [Journal Article] Numb has distinct function in lung adenocarcinoma and squamous cell carcinoma (2018)
  • Author(s): Kikuchi Hajime、Sakakibara-Konishi Jun、Furuta Megumi、Kikuchi Eiki、Kikuchi Junko、Oizumi Satoshi、Hida Yasuhiro、Kaga Kichizo、Kinoshita Ichiro、Dosaka-Akita Hirotoshi、Nishimura Masaharu
  • Journal Title: Oncotarget Volume: 9 Issue: 50 Pages: 29379-29391
  • DOI: 10.18632/oncotarget.25585
  • Peer Reviewed
• [Presentation] Analysis of DLL3 and ASCL1 in surgically resected small cell lung cancer (HOT1702) (2019)
  • Author(s): Megumi Furuta, Jun Sakakibara-Konishi, Hajime Kikuchi,
  • Organizer: AACR
  • Int'l Joint Research
• [Presentation] 小細胞肺癌切除検体におけるDLL3、ASCL1に関する検討 (2019)
  • Author(s): 峯村 浩之、古田 恵、榊原 純
  • Organizer: 日本呼吸器学会総会
• [Presentation] Analysis of DLL3 and ASCL1 in surgically resected small cell lung cancer (HOT1702) (2019)
  • Author(s): Masao Harada, Megumi Furuta, Jun Sakakibara-Konishi
  • Organizer: 日本臨床腫瘍学会総会
• [Presentation] DLL3 regulates migration and invasion of Small Cell Lung Cancer (2018)
  • Author(s): Megumi Furuta1, Jun Sakakibara-Konishi1, Tetsuaki Shoji1, Yuta Takashima1, Hajime Kikuchi 1, Eiki Kikuchi1, Junko Kikuchi1, Ichiro Kinoshita2, Hirotoshi Dosaka-Akita2, Masaharu Nishimura1
  • Organizer: AACR
  • Int'l Joint Research