医学部 分子腫瘍学

鈴木 元

Motoshi Suzuki

基本情報

所属
藤田医科大学 医学部 医学科 教授 (医学研究科副研究科長)
学位
医学博士(名古屋大学)

J-GLOBAL ID
200901026349208170
researchmap会員ID
1000023596

外部リンク

論文

 154
  • Atsuko Niimi, Siripan Limsirichaikul, Keiko Kano, Yasuyoshi Mizutani, Toshiyuki Takeuchi, Patinya Sawangsri, Dat Quoc Tran, Yoshiyuki Kawamoto, Motoshi Suzuki
    Cancers 15(10) 2781-2781 2023年5月16日  
    CERS6 is associated with metastasis and poor prognosis in non-small cell lung cancer (NSCLC) patients through d18:1/C16:0 ceramide (C16 ceramide)-mediated cell migration, though the detailed mechanism has not been elucidated. In the present study, examinations including co-immunoprecipitation, liquid chromatography, and tandem mass spectrometry analysis were performed to identify a novel binding partner of CERS6. Among the examined candidates, LASP1 was a top-ranked binding partner, with the LIM domain possibly required for direct interaction. In accord with those findings, CERS6 and LASP1 were found to co-localize on lamellipodia in several lung cancer cell lines. Furthermore, silencing of CERS6 and/or LASP1 significantly suppressed cell migration and lamellipodia formation, whereas ectopic addition of C16 ceramide partially rescued those phenotypes. Both LASP1 and CERS6 showed co-immunoprecipitation with actin, with those interactions markedly reduced when the LASP1–CERS6 complex was abolished. Based on these findings, it is proposed that LASP1–CERS6 interaction promotes cancer cell migration.
  • Mika Iwai, Taisuke Kajino, Masahiro Nakatochi, Kiyoshi Yanagisawa, Yasuyuki Hosono, Hisanori Isomura, Yukako Shimada, Motoshi Suzuki, Ayumu Taguchi, Takashi Takahashi
    Oncogene 2022年12月15日  
    Non-coding RNAs have an integral regulatory role in numerous functions related to lung cancer development. Here, we report identification of a novel lncRNA, termed TP53-inhibiting lncRNA (TILR), which was found to function as a constitutive negative regulator of p53 expression, including activation of downstream genes such as p21 and MDM2, and induction of apoptosis. A proteomic search for TILR-associated proteins revealed an association with PCBP2, while the mid-portion of TILR was found to be required for both PCBP2 and p53 mRNA binding. In addition, depletion of PCBP2 resulted in phenocopied effects of TILR silencing. TILR was also shown to suppress p53 expression in a post-transcriptional manner, as well as via a positive feedback loop involving p53 and Fanconi anemia pathway genes. Taken together, the present findings clearly demonstrate that TILR constitutively inhibits p53 expression in cooperation with PCBP2, thus maintaining p53 transcriptional activity at a level sufficiently low for avoidance of spurious apoptosis induction.
  • Yasuyoshi Mizutani, Kazuya Shiogama, Ken-Ichi Inada, Toshiyuki Takeuchi, Atsuko Niimi, Motoshi Suzuki, Yutaka Tsutsumi
    Acta histochemica et cytochemica 55(5) 129-148 2022年10月28日  
    The enzyme-labeled antigen method is an immunohistochemical technique detecting plasma cells producing specific antibodies in tissue sections. The probe is an antigen labeled with an enzyme or biotin. This immunohistochemical technique is appliable to frozen sections of paraformaldehyde (PFA)-fixed tissues, but it has been difficult to apply it to formalin-fixed, paraffin-embedded (FFPE) sections. In the current study, factors inactivating the antibody reactivity during the process of preparing FFPE sections were investigated. Lymph nodes of rats immunized with horseradish peroxidase (HRP) or a mixture of keyhole limpet hemocyanin/ovalbumin/bovine serum albumin were employed as experimental models. Plasma cells producing specific antibodies, visualized with HRP (as an antigen with enzymatic activity) or biotinylated proteins in 4% PFA-fixed frozen sections, significantly decreased in unbuffered 10% formalin-fixed frozen sections. The positive cells were further decreased by paraffin embedding following formalin fixation. In paraffin-embedded sections fixed in precipitating fixatives such as ethanol and acetone and those prepared with the AMeX method, the antigen-binding reactivity of antibodies was preserved. Fixation in periodate-lysine-paraformaldehyde and Zamboni solution also kept the antigen-binding reactivity in paraffin to some extent. In conclusion, formalin fixation and paraffin embedding were major causes inactivating antibodies. Precipitating fixatives could retain the antigen-binding reactivity of antibodies in paraffin-embedded sections.
  • Masanobu Saruta, Kiyoshi Takahara, Atsuhiko Yoshizawa, Atsuko Niimi, Toshiyuki Takeuchi, Takuhisa Nukaya, Masashi Takenaka, Kenji Zennami, Manabu Ichino, Hitomi Sasaki, Mamoru Kusaka, Motoshi Suzuki, Makoto Sumitomo, Ryoichi Shiroki
    Journal of clinical medicine 11(18) 2022年9月16日  
    Alanine-serine-cysteine transporter 2 (ASCT2) has been associated with increased levels of metabolism in various malignant tumors. However, its biological significance in the proliferation of prostate cancer (PCa) cells remains under investigation. We used the cBioPortal database to assess the effect of ASCT2 expression on the oncological outcomes of 108 PCa patients. To evaluate the function of ASCT2 in castration-sensitive PCa (CSPC) and castration-resistant PCa (CRPC), LNCaP cells and the ARV7-positive PCa cell line, 22Rv1, were assessed using cell proliferation assays and Western blot analyses. The ASCT2 expression level was associated with biochemical recurrence-free survival after prostatectomy in patients with a Gleason score ≥ 7. In vitro experiments indicated that the growth of LNCaP cells after combination therapy of ASCT2 siRNA and enzalutamide treatment was significantly reduced, compared to that following treatment with enzalutamide alone or ASCT2 siRNA transfection alone (p < 0.01, 0.01, respectively). After ASCT2 inhibition by siRNA transfection, the growth of 22Rv1 cells was significantly suppressed as compared with negative control siRNA via downregulation of ARV7 both in fetal bovine serum and androgen-deprivation conditions (p < 0.01, 0.01, respectively). We demonstrated that ASCT2 inhibition significantly reduced the proliferation rates of both CSPC and CRPC cells in vitro.
  • 前田 真男, 西尾 永司, 林 孝典, ベフヌーシュ・ハレディアン, 牛田 かおり, 岡田 誠治, 鈴木 元, 浅井 直也, 藤井 多久磨, 佐谷 秀行, 下野 洋平
    日本癌学会総会記事 81回 P-2287 2022年9月  

MISC

 19

共同研究・競争的資金等の研究課題

 29