Analysis of molecular function of S100A14 and its clinical aplication to diagnosis and therapy of breast cancer.

• Project/Area Number: 24501318
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Shizuoka Cancer Center Research Institute
• Principal Investigator: SUGINO Takashi 静岡県立静岡がんセンター(研究所), その他部局等, その他 (90171165)
• Co-Investigator(Renkei-kenkyūsha): TANAKA Mizuko 福島県立医科大学, 医学部, 助教 (40583638) ; TOMIKAWA Naoki 福島県立医科大学, 医学部, 講師 (80468587) ; CHIBA Hideki 福島県立医科大学, 医学部, 教授 (00295346)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: S100A14 / S100A16 / 乳癌 / 予後 / 浸潤 / 細胞運動 / がん転移 / 転移 / 予後因子

Outline of Final Research Achievements

S100 family proteins have recently been identified as biomarkers in various cancers. The aim of the present study was to clarify the clinical significance and functional role of S100A14 in breast cancer. Immunohistochemical analysis of 167 breast cancer cases showed that higher expression levels of the proteins was significantly associated with a poorer prognosis. In the human breast cancer cell lines, S100A14 protein was colocalized on the cell membrane. Experimental analyses demonstrated that the S100A14 protein can bind to actin. A Boyden chamber assay showed that S100A14 knockdown suppressed the invasive activity. We demonstrated that coexpression of S100A14 and S100A16 correlates with poor prognosis of breast cancer patients. In addition, our findings indicate that these proteins can promote invasive activity of breast cancer cells via an interaction with cytoskeletal dynamics.

Research Products

• [Journal Article] Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the suppression of osteoclastogenesis in head and neck squamous carcinoma. (2018)
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• [Journal Article] Obvious Pitfall in the Estimation of Renal Dysfunction. (2016)
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• [Journal Article] Abhydrolase domain containing 2, an androgen target gene, promotes prostate cancer cell proliferation and migration (2016)
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  • Journal Title: European Journal of Cancer Volume: 49 Pages: 1715-1724
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• [Journal Article] Co-expression of S100A14 and S100A16 correlates with a poor prognosis in human breast cancer and promotes cancer cell invasion (2015)
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  • DOI: 10.1186/s12885-015-1059-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Immunologically augmented skin flap as a novel dendritic cell vaccine against head and neck cancer in a rat model (2015)
  • Author(s): Inoue K, Saegusa N, Omiya M, Ashizawa T, Miyata H, Komiyama M, Iizuka A, Kume A, Sugino T, Yamaguchi K, Kiyohara Y, Nakagawa M, Akiyama Y.
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• [Journal Article] Aberrant differentiation of Tsc2-deficient teratomas associated with activation of the mTORC1-TFE3 pathway. (2015)
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  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Establishment of highly metastatic cell line (Lu10) from murine mammary carcinoma cell line MCH66 and biological characteristics of Lu10. (2014)
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• [Journal Article] YKL-40 downregulation is a key factor to overcome temozolomide resistance in a glioblastoma cell line (2014)
  • Author(s): Akiyama Y, Ashizawa T, Komiyama M, Miyata H, Oshita C, Omiya M, Iizuka A, Kume A, Sugino T, Hayashi N, Mitsuya K, Nakasu Y, Yamaguchi K.
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  • DOI: 10.3892/or.2014.3195
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Effect of the STAT3 inhibitor STX-0119 on the proliferation of a temozolomide-resistant glioblastoma cell line (2014)
  • Author(s): Ashizawa T, Akiyama Y, Miyata H, Iizuka A, Komiyama M, Kume A, Omiya M, Sugino T, Asai A, Hayashi N, Mitsuya K, Nakasu Y, Yamaguchi K.
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• [Journal Article] Discovery of an uncovered region in fibrin clots and its clinical significance (2013)
  • Author(s): Hisada Y, Yasunaga M, Hanaoka S, Saijou S, Sugino T, Tsuji A, Saga T, Tsumoto K, Manabe S, Kuroda J, Kuratsu J, Matsumura Y.
  • Journal Title: SCIENTIFIC REPORTS Volume: 3 Pages: 2604-2604
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• [Journal Article] Potential for respiratory epithelium regeneration from induced pluripotent stem cells. (2013)
  • Author(s): Otsuki K, Imaizumi M, Nomoto Y, Wada I, Miyake M, Sugino T, Omori K.
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• [Journal Article] Implantation site-dependent differences for tracheal regeneration with induced pluripotent stem cells (iPS cells). (2013)
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• [Journal Article] Evaluation of the use of induced pluripotent stem cells (iPSCs) for the regeneration of tracheal cartilage. (2013)
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  • Journal Title: Cell Transplantation. Volume: 22 Pages: 341-353
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• [Journal Article] α-type-1 polarized dendritic cell-based vaccination in recurrent high-grade glioma: a phase I clinical trial (2012)
  • Author(s): Akiyama Y, Oshita C, Kume A, Iizuka A, Miyata H, Komiyama M, Ashizawa T, Yagoto M, Abe Y, Mitsuya K, Watanabe R, Sugino T, Yamaguchi K, Nakasu Y.
  • Journal Title: BMC Cancer Volume: 27;12 Pages: 1-10
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• [Journal Article] A combination of liposomal sunitinib plus liposomal irinotecan and liposome co-loaded with two drugs enhanced antitumor activity in PC12-bearing mouse. (2012)
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  • Journal Title: J Drug Target Volume: 20(10) Pages: 873-882
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• [Journal Article] Interphase cytogenetic analysis of lung adenocarcinomas with bronchioloalveolar pattern. (2012)
  • Author(s): Shimizu H, Sugino T, Chiba H.
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  • NAID: 130002153561
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• [Journal Article] Case of primary central nervous system lymphoma after open head injury (2012)
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  • Journal Title: Rinsho Shinkeigaku Volume: 52(5) Pages: 329-335
  • NAID: 130004505261
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• [Journal Article] Malignant mixed Müllerian tumor of the fallopian tube: a case report. (2012)
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• [Journal Article] Analysis of chromosome 19q13.42 amplification in embryonal brain tumors with ependymoblastic multilayered rosettes. (2012)
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• [Journal Article] Production of IL1-beta by ovarian cancer cells induces mesothelial cell beta1-integrin expression facilitating peritoneal dissemination. (2012)
  • Author(s): Watanabe T, Hashimoto T, Sugino T, Soeda S, Nishiyama H, Morimura Y, Yamada H, Goodison S, Fujimori K.
  • Journal Title: J Ovarian Res Volume: 5(1) Pages: 7-7
  • DOI: 10.1186/1757-2215-5-7
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• [Presentation] Expression of S100A14 promotes cancer cell invasion and metastasis and is associated with poor prognosis in breast cancer (2014)
  • Author(s): Takashi Sugino, Mizuko Tanaka, Takuma Oishi and Takashi Nakajima
  • Organizer: 37th Annual San Antonio Breast Cancer Symposium
  • Place of Presentation: San Antonio, USA
  • Year and Date: 2014-12-09 – 2014-12-13
• [Presentation] マウス転移モデルの作製とmicroarray, in vivo knockdownを用いた転移関連分子の同定
  • Author(s): 杉野隆、千葉英樹、中島孝
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] マウス乳癌転移モデルの開発と転移関連遺伝子の探索
  • Author(s): 宍戸奈美子、田中瑞子、冨川直樹、千葉英樹、杉野隆
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌