Functional analysis of a novel signal molecule CDCP1 which regulates anchorage-independent growth in cancer cells

• Project/Area Number: 21590350
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East
• Principal Investigator: UEKITA Takamasa 独立行政法人国立がん研究センター, 研究所, 主任研究員 (50373402)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: CDCP1 / 足場非依存性 / 細胞運動能 / 浸潤 / MMP / 足場非依存性増殖 / がんの浸潤 / 細胞間接着

Research Abstract

In this study, we found the three functions of CDCP1 in cancer cells. First, CUB2 and CUB3 in the extracellular domain of CDCP1 and the region including Tyrosine734 in the intracellular domain of CDCP1 might contribute to regulate anchorage-independent growth in cancer cell. Second, CDCP1 regulates cancer invasion through regulation of MMP-9 secretion and membranous transportation of MT1-MMP to invadopodia. Finally, induction of CDCP1 expression by Ras along with tyrosine phosphorylation of CDCP1 by Src family kinases is required for Ras-mediated oncogenic phenotypes, such as anchorage-independent growth, invasion and metastasis.

Research Products

• [Journal Article] Roles of CUB domain-containing protein 1 signaling in cancer invasion and metastasis (2011)
  • Author(s): Uekita T. and Sakai R
  • Journal Title: Cancer Sci Volume: 102 Issue: 11 Pages: 1943-1948
  • DOI: 10.1111/j.1349-7006.2011.02052.x
  • NAID: 10030244592
  • Peer Reviewed
• [Journal Article] Roles of CUB domain-containing protein 1 signaling in cancer invasion and metastasis (2011)
  • Author(s): Tkamasa Uekita, Ryuichi Sakai
  • Journal Title: Cancer Science Volume: 102 Pages: 1943-1948
  • NAID: 10030244592
  • Peer Reviewed
• [Journal Article] CUB domain-containing protein 1, a prognostic factor for human pancreatic cancers, promotes cell migration and extracellular matrix degradation (2010)
  • Author(s): Miyazawa Y., Uekita T., Hiraoka N., Fujii S., Kosuge T., Kanai Y., Nojima Y. and Sakai R.
  • Journal Title: Cancer Res Volume: 70 Issue: 12 Pages: 5136-5146
  • DOI: 10.1158/0008-5472.can-10-0220
  • Peer Reviewed
• [Journal Article] CUB domain-containing protein 1, a prognostic factor for human pancreatic cancers, promotes cell migration and extracellular matrix degradation. (2010)
  • Author(s): Y.Miyazawa, T.Uekita, et al., 他6名
  • Journal Title: Cancer Research Volume: 70 Pages: 5136-5146
  • Peer Reviewed
• [Journal Article] CUB Domain-Containing Protein 1, a Prognostic Factor for Human Pancreatic Cancers, Promotes Cell Migration and Extracellular Matrix Degradation (2010)
  • Author(s): Y.Miyazawa, T.Uekita, et al.(他6名)
  • Journal Title: Cancer Research 70(in press)
  • Peer Reviewed
• [Journal Article] Expression of CUB domain containing protein(CDCP1) is correlated with prognosis and survival of patients with adenocarcinoma of lung (2009)
  • Author(s): Ikeda JI., Oda T., Inoue M., Uekita T., Sakai R., Okumura M., Aozasa K. and Morii E.
  • Journal Title: Cancer Sci Volume: 100 Issue: 3 Pages: 429-433
  • DOI: 10.1111/j.1349-7006.2008.01066.x
  • NAID: 10025143186
  • Peer Reviewed
• [Journal Article] Expression of CUB domain containing protein(CDCP1)is correlated with prognosis and survival of patients with adenocarcinoma of lung (2009)
  • Author(s): J.Ikeda, T.Uekita, E.Morii, et al.(他4名)
  • Journal Title: Cancer Science 100 Pages: 429-433
  • NAID: 10025143186
  • Peer Reviewed
• [Presentation] 癌の足場非依存性と浸潤・転移を制御する新規因子CDCP1の解析 (2012)
  • Author(s): 上北尚正、堺隆一
  • Organizer: 平成23年度「個体レベルでのがん研究支援活動」ワークショップ個体レベルのがん研究のパラダイム-動物発がんモデルと分子機構の解明-
  • Place of Presentation: 琵琶湖ホテル
  • Year and Date: 2012-01-19
• [Presentation] 癌の足場非依存性と浸潤・転移を制御する新規因子CDCP1の解析 (2012)
  • Author(s): 上北尚正、堺隆一
  • Organizer: 平成23年度「個体レベルでのがん研究支援活動」ワークショップ個体レベルのがん研究のパラダイムー動物発がんモデルと分子機構の解明-
  • Place of Presentation: 琵琶湖ホテル、滋賀県大津市
  • Year and Date: 2012-01-19
• [Presentation] Suppression of autophagy by CDCP1 is essential for anoikis resistance in cancer cells (2011)
  • Author(s): Uekita T. and Sakai R
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-05
• [Presentation] Suppression of autophagy by CDCP1 is essential for anoikis resistance in cancer cells (2011)
  • Author(s): Takamasa Uekita, Ryuichi Sakai
  • Organizer: 70^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: NAGOYA CONGRESS CENTER, Nagoya, Japan
  • Year and Date: 2011-10-05
• [Presentation] CDCP1 links Ras and Src signaling pathway as a common effector for the promotion of tumor metastasis (2011)
  • Author(s): Uekita T. and Sakai R
  • Organizer: The 6th Mechanisms & Models of Cancer
  • Place of Presentation: Salk
  • Year and Date: 2011-08-14
• [Presentation] CDCP1 Links Ras and Src Signaling Pathway as a Common Effector for the Promotion of Tumor Metastasis (2011)
  • Author(s): Takamasa Uekita, Ryuichi Sakai
  • Organizer: The 6^<th> Mechanisms & Models of Cancer
  • Place of Presentation: Salk Inst., La Jolla, CA, USA
  • Year and Date: 2011-08-14
• [Presentation] Oncogenic Ras induces CDCP1 expression and regulates anoikis resistance, motility and invasion in cancer cells (2010)
  • Author(s): Uekita T. and Sakai R
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場・リーガロイヤルホテル
  • Year and Date: 2010-09-23
• [Presentation] Oncogenic Ras induces CDCP1 expression and regulates anoikis resistance, motility and invasion in cancer cells (2010)
  • Author(s): Takamasa Uekita, Ryuichi Sakai, et al., 他2名
  • Organizer: 69^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Osaka international Convention Center RIHGA Royal Hotel Osaka
  • Year and Date: 2010-09-23
• [Presentation] がん細胞の浸潤に関与するCDCP1及び下流因子PKCδの機能解析 (2010)
  • Author(s): 宮澤悠里、上北尚正、堺隆一
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場・リーガロイヤルホテル
  • Year and Date: 2010-09-22
• [Presentation] 肺がんの骨転移モデル作製と骨転移関連因子の探索 (2010)
  • Author(s): 八木玲子、上北尚正、堺隆一
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場・リーガロイヤルホテル
  • Year and Date: 2010-09-22
• [Presentation] 癌細胞の足場非依存性増殖におけるCDCP1のAutophagy抑制の重要性 (2010)
  • Author(s): 上北尚正、堺隆一
  • Organizer: 第19回日本がん転移学会学術集会・総会
  • Place of Presentation: 金沢市文化ホール
  • Year and Date: 2010-06-17
• [Presentation] Regulation of metastasis and invasion by a novel Src substrate CDCP1 (2009)
  • Author(s): Uekita T. and Sakai R
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-10-03
• [Presentation] Regulation of metastasis and invasion by a novel Src substrate CDCP1 (2009)
  • Author(s): Takamasa Uekita, Ryuichi Sakai
  • Organizer: 68^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: PACIFICO YOKOHAMA
  • Year and Date: 2009-10-03
• [Presentation] CDCP1は膵癌の転移・浸潤能に関わる予後因子である (2009)
  • Author(s): 上北尚正、堺隆一
  • Organizer: 第18回日本がん転移学会学術集会・総会
  • Place of Presentation: 旭川グランドホテル
  • Year and Date: 2009-07-24
• [Remarks]
  • URL: http://www.ncc.go.jp/jp/nccri/divisions/07grow/07grow.html