CD271 is a functional and therapeutic-targetable marker of cell proliferation in hypopharyngeal cancer.

• Project/Area Number: 16K20290
• 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: Mochizuki Mai 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), がん幹細胞研究部, 研究員 (40726303)
• Research Collaborator: Imai Takayuki ; Matsuura Kazuto
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 下咽頭癌 / CD271 / 細胞増殖 / 細胞周期 / 下咽頭がん / 癌

Outline of Final Research Achievements

We previously reported that CD271 (p75 neurotrophin receptor) is expressed in invasive front and a marker for tumor formation and is correlated with a poor prognosis in human hypopharyngeal cancer (HPC). To elucidate the role of CD271 in HPC, we established HPC cell lines and CD271-knockdown cells using siRNA. We found that CD271-knockdown completely suppressed the cells’ tumor-forming capability both in vivo and in vitro. CD271-knockdown induced cell-cycle arrest and CDKN1C expression, whereas suppressed ERK phosphorylation. In addition, either CD271 depletion diminished the in vitro migration capability. Collectively, CD271 initiates tumor formation by increasing the cell proliferation capacity through CDKN1C suppression and ERK-signaling activation, and by accelerating the migration signaling pathway in HPC.

Academic Significance and Societal Importance of the Research Achievements

本研究は、従来有望な治療標的に乏しかった下咽頭癌に焦点を当て、CD271という分子が癌の増殖・遊走能の制御に関与することを新規に見出した。さらに、申請者はCD271の下流で細胞周期制御分子であり、がん抑制因子としても知られるCDKN1Cが抑制されることを見出しており、癌の悪性化の要因の一つである可能性を示した。これらの結果は、CD271を標的とした治療の有望性を示しており、今後さらに研究を進めることで新規治療法の開発に弾みがつくと考えられる。

Research Products

• [Journal Article] Periostin attenuates tumor growth by inducing apoptosis in colitis-related colorectal cancer (2018)
  • Author(s): Shimoyama Yusuke、Tamai Keiichi、Shibuya Rie、Nakamura Mao、Mochizuki Mai、Yamaguchi Kazunori、Kakuta Yoichi、Kinouchi Yoshitaka、Sato Ikuro、Kudo Akira、Shimosegawa Tooru、Satoh Kennichi
  • Journal Title: Oncotarget Volume: 9 Issue: 28 Pages: 20008-20017
  • DOI: 10.18632/oncotarget.25026
  • Peer Reviewed / Open Access
• [Journal Article] Periostin is a negative prognostic factor and promotes cancer cell proliferation in non-small cell lung cancer (2018)
  • Author(s): Okazaki Toshimasa、Tamai Keiichi、Shibuya Rie、Nakamura Mao、Mochizuki Mai、Yamaguchi Kazunori、Abe Jiro、Takahashi Satomi、Sato Ikuro、Kudo Akira、Okada Yoshinori、Satoh Kennichi
  • Journal Title: Oncotarget Volume: 9 Issue: 58 Pages: 31187-31199
  • DOI: 10.18632/oncotarget.25435
  • Peer Reviewed / Open Access
• [Journal Article] Long non-coding RNA HOTAIR up?regulates chemokine (C?C motif) ligand 2 and promotes proliferation of macrophages and myeloid?derived suppressor cells in hepatocellular carcinoma cell lines (2018)
  • Author(s): Fujisaka Yasuyuki、Iwata Tomoaki、Tamai Keiichi、Nakamura Mao、Mochizuki Mai、Shibuya Rie、Yamaguchi Kazunori、Shimosegawa Tooru、Satoh Kennichi
  • Journal Title: Oncology Letters Volume: 15 Pages: 509-514
  • DOI: 10.3892/ol.2017.7322
  • Peer Reviewed / Open Access
• [Journal Article] Long non-coding RNA HOTAIR promotes cell migration by upregulating insulin growth factor?binding protein 2 in renal cell carcinoma (2017)
  • Author(s): Katayama Hiromichi、Tamai Keiichi、Shibuya Rie、Nakamura Mao、Mochizuki Mai、Yamaguchi Kazunori、Kawamura Sadafumi、Tochigi Tatsuo、Sato Ikuro、Okanishi Takamasa、Sakurai Kunie、Fujibuchi Wataru、Arai Yoichi、Satoh Kennichi
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 12016-12016
  • DOI: 10.1038/s41598-017-12191-z
  • NAID: 120006364089
  • Peer Reviewed / Open Access
• [Journal Article] CD271 regulates the proliferation and motility of hypopharyngeal cancer cells (2016)
  • Author(s): Mochizuki M, Tamai K, Imai T, Sugawara S, Ogama N, Nakamura M, Matsuura K, Yamaguchi K, Satoh K, Sato I, Motohashi H, Sugamura K, Tanaka N
  • Journal Title: Sci Reｐ Volume: 6 Issue: 1 Pages: 30707-30707
  • DOI: 10.1038/srep30707
  • Peer Reviewed / Open Access
• [Journal Article] Xenotransplantation elicits salient tumorigenicity of adult T-cell leukemia-derived cells via aberrant AKT activation. (2016)
  • Author(s): Yamaguchi K, Takanashi T, Nasu K, Tamai K, Mochizuki M, Satoh I, Ine S, Sasaki O, Satoh K, Tanaka N, Harigae H, Sugamura K.
  • Journal Title: Cancer Sci. Volume: ePub Issue: 5 Pages: 638-643
  • DOI: 10.1111/cas.12921
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 肺扁平上皮癌の増殖はCD271依存性である (2018)
  • Author(s): 望月麻衣
  • Organizer: 第77回日本癌学会学術総会
• [Presentation] Lung squamous cell carcinoma exclusively depends on CD271 for cell proliferation. (2018)
  • Author(s): Mai Mochizuki et. al.
  • Organizer: Mechanisms & models of cancer
  • Int'l Joint Research
• [Presentation] 頭頸部癌においてCD271は増殖・浸潤を制御する (2016)
  • Author(s): 望月麻衣,玉井恵一,等
  • Organizer: 第３９回日本分子生物学会総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30