Roles of TGF-beta target genes TMEPAI and MafK on cancer development

• Project/Area Number: 25293092
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: University of Tsukuba
• Principal Investigator: Kato Mitsuyasu 筑波大学, 医学医療系, 教授 (20194855)
• Co-Investigator(Renkei-kenkyūsha): WATANABE Yukihide 筑波大学, 医学医療系, 助教 (40618534) ; OKITA Yukari 筑波大学, 医学医療系, 研究員 (30743710)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: がん / 足場非依存性増殖 / がん幹細胞 / トランスフォーミング増殖因子β / TGF-β / TMEPAI / MafK / GPNMB / 特殊環状ペプチド / MAFK / 上皮間葉転換 / 幹細胞 / Gpnmb

Outline of Final Research Achievements

Transforming Growth Factor-β (TGF-β) was discovered as a factor expressed by oncogenes and induces anchorage-independent soft agar colony formation together with TGF-α. In this study, we identified TMEPAI and MafK as target genes expressed by TGF-β and induces anchorage-independent growth and tumor formation. TMEPAI suppresses TGF-β/Smad signaling and activates AKT. MafK induces epithelial-mesenchymal transition and transmembrane glycoprotein GPNMB. These activities are essential for their tumorigenic activities. We further made antibodies for TMEPAI and MafK for further clinic-pathological studies.

Research Products

• [Journal Article] Regulation of the TMEPAI promoter by TCF7L2: the C-terminal tail of TCF7L2 is essential to activate the TMEPAI gene (2016)
  • Author(s): Naoko Nakano, Mitsuyasu Kato & Susumu Itoh
  • Journal Title: The journal of biochemistry Volume: 159 Issue: 1 Pages: 27-30
  • DOI: 10.1093/jb/mvv117
  • NAID: 120007129718
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cooperative induction of transmembrane prostate androgen induced protein TMEPAI/PMEPA1 by transforming growth factor-b and epidermal growth factor signaling. (2015)
  • Author(s): Azami S, Vo Nguyen TT, Watanabe Y, Kato M.
  • Journal Title: Biochem Biophys Res Commun. Volume: 456 Issue: 2 Pages: 580-585
  • DOI: 10.1016/j.bbrc.2014.11.107
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] C18ORF1: A Novel Negative Regulator of TGF-β Signaling. (2014)
  • Author(s): 2. Nakano N, Maeyama K, Ikeno S, Itoh F, Togawa Y, Katsu Y, Thanh Thao, VN, Watanabe Y, Kato M & Itoh, S.
  • Journal Title: J. Biol. Chem., Volume: 289 Issue: 18 Pages: 12680-12680
  • DOI: 10.1074/jbc.m114.558981
  • Peer Reviewed
• [Journal Article] TMEPAI/PMEPA1 enhances tumorigenic activities in lung cancer cells. (2014)
  • Author(s): 3) Vo Nguyen TT, Watanabe Y, Shiba A, Noguchi M, Itoh S and Kato M.
  • Journal Title: Cancer Sci. Volume: 105 Issue: 3 Pages: 334-341
  • DOI: 10.1111/cas.12355
  • NAID: 120007136725
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] C18 ORF1: A Novel Negative Regulator of TGF-β Signaling. (2014)
  • Author(s): Nakano N, Maeyama K, Sakata N, Itoh F, Akatsu R, Nakata M, Katsu Y, Ikeno S, Togawa Y, Thanh Thao Vo Nguyen TT, Watanabe Y, Kato M and Itoh S.
  • Journal Title: Jounal of Biological Chemistry Volume: 289
  • Peer Reviewed
• [Journal Article] Transforming growth factor-&βinduces transcription factors MafK and Bach1 to suppress expression of the heme oxygenase-1 gene. (2013)
  • Author(s): Okita Y, Kamoshida A, Suzuki H, Itoh K, Motohashi H, Igarashi K, Ogami T, Koinuma D, Kato M.
  • Journal Title: J Biol Chem Volume: 288 Issue: 28 Pages: 20658-20667
  • DOI: 10.1074/jbc.m113.450478
  • NAID: 120007136878
  • Peer Reviewed
• [Journal Article] Activin receptor-like kinase5 inhibition suppresses mouse melanoma by ubiquitin degradation of Smad4, thereby derepressing eomesodermin in cytotoxic T lymphocytes (2013)
  • Author(s): Yoon JH, Sudo K, Kuroda M. (18 名 15 番目)
  • Journal Title: EMBO molecular Medicine Volume: 5(11) Issue: 11 Pages: 1720-39
  • DOI: 10.1002/emmm.201302524
  • Peer Reviewed
• [Presentation] 扁平上皮がんの発生におけるTHG-1の機能 (2015)
  • Author(s): 鈴木裕之
  • Organizer: 第23回翠嶂会セミナー（つくば）
  • Place of Presentation: 筑波山ホテル青木屋
  • Year and Date: 2015-10-31
• [Presentation] ADPリボース化によるBMPシグナルの制御 (2015)
  • Author(s): 渡邊幸秀、Aristidis Moustakas、加藤光保
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-10-08
• [Presentation] 乳がんにおける転写因子MafKの働き (2015)
  • Author(s): 沖田結花里、鈴木裕之、加藤光保
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-10-08
• [Presentation] 腫瘍の血管新生におけるTHG-1/Tsc22D4の役割 (2015)
  • Author(s): LING ZHENG、鈴木裕之、加藤光保
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-10-08
• [Presentation] Roles of MafK and Gpnmb in tumor development. (2015)
  • Author(s): Mitsuyasu Kato
  • Organizer: TGF-β meeting 2015
  • Place of Presentation: Uppsala, Sweden
  • Year and Date: 2015-08-20
• [Presentation] Role of THG-1/Tsc22D4 in tumor angiogenesis. (2015)
  • Author(s): Ling Zheng
  • Organizer: TGF-β meeting 2015
  • Place of Presentation: Uppsala, Sweden
  • Year and Date: 2015-08-20
• [Presentation] Transcription factor MafK induces epithelial-mesenchymal transition and malignant progression of breast cancer cells. (2015)
  • Author(s): Yukari Okita, Hiroyuki Suzuki and Mitsuyasu Kato
  • Organizer: FASEB Science Research Conference
  • Place of Presentation: Snowmass, Colorado
  • Year and Date: 2015-07-12
• [Presentation] 大腸腫瘍の発生に置ける間欠性増殖細胞の動態に関する研究 (2015)
  • Author(s): 加藤光保
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-04-30
• [Presentation] 扁平上皮がんの進展におけるTHG-1/Tsc22D4の役割 (2015)
  • Author(s): 小沼雅世
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-04-30
• [Presentation] 乳がん細胞におけるGpnmb発現制御機構の解析 (2015)
  • Author(s): 木村美範
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-04-30
• [Presentation] 乳がんにおける転写因子MafKの役割 (2014)
  • Author(s): 沖田結花里
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] 腫瘍の血管新生におけるTHG-1/Tsc22D4の役割 (2014)
  • Author(s): 鄭齢
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] TEMPAI enhances Tumorigenic Activities in Lung Cancer Cells (2014)
  • Author(s): Vo Nguyen Thanh Thao
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] がんの発生と進展における トランスフォーミング増殖因子β の作用 (2013)
  • Author(s): 加藤光保
  • Organizer: 第10回日本病理学会カンファレンス
  • Place of Presentation: 神戸
  • Invited
• [Presentation] Tumorigenic activities of TGF-β Target Genes TMEPAI and MafK (2013)
  • Author(s): Mitsuyasu Kato
  • Organizer: TGF-β meeting in Uppsala
  • Place of Presentation: Uppsala, Sweden
  • Invited
• [Presentation] Tumorigenic activity of TMEPAI and MafK (2013)
  • Author(s): Mitsuyasu Kato
  • Organizer: The 3rd International Symposium by JSPS Core-to-Core Program “Cooperative International Framework in TGF-β Family Signaling”
  • Place of Presentation: 松山
  • Invited
• [Presentation] 乳腺上皮細胞の上皮間葉転換と腫瘍形成における小Maf群転写因子の役割 (2013)
  • Author(s): 沖田結花里
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌
• [Presentation] 乳腺細胞の上皮間葉転換と腫瘍形成における転写因子MafKの役割 (2013)
  • Author(s): 沖田結花里
  • Organizer: 第32回分子病理学研究会
  • Place of Presentation: 奈良