Development a novel therapy for hepatocellular carcinoma by targeting STEAP1
| Project/Area Number |
19K08397
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中村 元 札幌医科大学, 医学部, 研究員 (10792666)
加藤 淳二 札幌医科大学, 医学部, 教授 (20244345)
宮西 浩嗣 札幌医科大学, 医学部, 准教授 (60372819)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | STEAP1 / HCC / c-Myc / 肝細胞癌 / 活性酸素種 |
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| Outline of Research at the Start |
切除不能HCCに対して治癒を期待できる薬物療法は確立されておらず，その予後は極めて不良である．申請者は，鉄代謝関連分子であるSTEAP1がHCCで過剰発現しており，STEAP1過剰発現群が予後不良であることをin silico 解析で明らかにしている．また，STEAP1がレドックス制御分子であるNRF2活性に関与している可能性も見出している．しかしながら，STEAP1による酸化ストレス制御機構およびSTEAP1がHCCの病態形成に関与しているか否かは不明である．本研究目的は，HCCにおけるSTEAP1/NRF2経路による酸化ストレス制御機構を解析する．
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| Outline of Final Research Achievements |
STEAP1 has emerged as an ideal target in cancer therapeutics. However, the functions of STEAP1 in hepatocellular carcinoma (HCC) remain unexplored. In the current study, we sought to characterize the biological roles of STEAP1 in HCC. STEAP1 transcripts are over-expressed and associated with poor clinical outcomes in patients with HCC in several publicly available datasets. STEAP1 silencing using small interfering RNA inhibited cell growth and was accompanied by G1 arrest induced by the suppression of cyclin D1 and the promotion of p27. STEAP1 silencing suppressed the expression of c-Myc, which we identified as a component in STEAP1 signal transduction by mining publicly available datasets, and confirmed this by PCR array. In conclusion, the knockdown of STEAP1 in HCC cells led to cell-growth inhibition involving G1 arrest by targeting the suppression of c-Myc. This study suggests a preclinical concept for STEAP1 as a druggable target in HCC.
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| Academic Significance and Societal Importance of the Research Achievements |
前立腺癌で同定され，多くの癌細胞で過剰発現している細胞表面蛋白質であるSix-transmembrane epithelial antigen of prostate 1（STEAP1）は，肝細胞癌(HCC)の病態形成にどのように関与しているかは不明であり，先駆性や独創性があると考えられた．
HCCの治療薬として様々な薬剤が臨床導入されているが，切除不能HCC患者の予後は不良である．より効果的なHCC治療薬を開発するために新規標的分子の探索が必要不可欠であり，社会的意義は高い．
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Report
(4 results)
Research Products
(8 results)
