Development a novel therapy for hepatocellular carcinoma by targeting STEAP1

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08397
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Takada Kohichi 札幌医科大学, 医学部, 講師 (90398321)
• 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)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: STEAP1 / HCC / c-Myc

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.

Free Research Field

腫瘍学

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．