Frontiers in Cell and Developmental Biology (Oct 2023)
Selective targeting of α7 nicotinic acetylcholine receptor by synthetic peptide mimicking loop I of human SLURP-1 provides efficient and prolonged therapy of epidermoid carcinoma in vivo
- O. V. Shlepova,
- O. V. Shlepova,
- M. A. Shulepko,
- V. O. Shipunova,
- V. O. Shipunova,
- M. L. Bychkov,
- I. D. Kukushkin,
- I. D. Kukushkin,
- I. A. Chulina,
- V. N. Azev,
- E. I. Shramova,
- V. A. Kazakov,
- A. M. Ismailova,
- Y. A. Palikova,
- V. A. Palikov,
- E. A. Kalabina,
- E. A. Shaykhutdinova,
- G. A. Slashcheva,
- E. A. Tukhovskaya,
- I. A. Dyachenko,
- A. N. Murashev,
- S. M. Deyev,
- S. M. Deyev,
- S. M. Deyev,
- M. P. Kirpichnikov,
- M. P. Kirpichnikov,
- Z. O. Shenkarev,
- Z. O. Shenkarev,
- Z. O. Shenkarev,
- E. N. Lyukmanova,
- E. N. Lyukmanova,
- E. N. Lyukmanova
Affiliations
- O. V. Shlepova
- NTI Center, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
- O. V. Shlepova
- Moscow Institute of Physics and Technology, National Research University, Dolgoprudny, Russia
- M. A. Shulepko
- Faculty of Biology, Shenzhen MSU-BIT University, Shenzhen, China
- V. O. Shipunova
- Moscow Institute of Physics and Technology, National Research University, Dolgoprudny, Russia
- V. O. Shipunova
- Immunology Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
- M. L. Bychkov
- NTI Center, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
- I. D. Kukushkin
- Moscow Institute of Physics and Technology, National Research University, Dolgoprudny, Russia
- I. D. Kukushkin
- Bioengineering Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
- I. A. Chulina
- Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia
- V. N. Azev
- Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia
- E. I. Shramova
- Immunology Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
- V. A. Kazakov
- Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia
- A. M. Ismailova
- Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia
- Y. A. Palikova
- Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia
- V. A. Palikov
- Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia
- E. A. Kalabina
- Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia
- E. A. Shaykhutdinova
- Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia
- G. A. Slashcheva
- Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia
- E. A. Tukhovskaya
- Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia
- I. A. Dyachenko
- Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia
- A. N. Murashev
- Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia
- S. M. Deyev
- Immunology Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
- S. M. Deyev
- Biomarker Research Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia
- S. M. Deyev
- Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
- M. P. Kirpichnikov
- Bioengineering Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
- M. P. Kirpichnikov
- Interdisciplinary Scientific and Educational School of Moscow University Molecular Technologies of the Living Systems and Synthetic Biology, Faculty of Biology, Lomonosov Moscow State University, Leninskie Gory, Moscow, Russia
- Z. O. Shenkarev
- NTI Center, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
- Z. O. Shenkarev
- Moscow Institute of Physics and Technology, National Research University, Dolgoprudny, Russia
- Z. O. Shenkarev
- 0Structural Biology Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
- E. N. Lyukmanova
- Faculty of Biology, Shenzhen MSU-BIT University, Shenzhen, China
- E. N. Lyukmanova
- Bioengineering Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
- E. N. Lyukmanova
- Interdisciplinary Scientific and Educational School of Moscow University Molecular Technologies of the Living Systems and Synthetic Biology, Faculty of Biology, Lomonosov Moscow State University, Leninskie Gory, Moscow, Russia
- DOI
- https://doi.org/10.3389/fcell.2023.1256716
- Journal volume & issue
-
Vol. 11
Abstract
α7-Type nicotinic acetylcholine receptor (α7-nAChR) promotes the growth and metastasis of solid tumors. Secreted Ly6/uPAR-Related Protein 1 (SLURP-1) is a specific negative modulator of α7-nAChR produced by epithelial cells. Here, we investigated mechanisms of antiproliferative activity of recombinant SLURP-1 in epidermoid carcinoma A431 cells and activity of SLURP-1 and synthetic 21 a.a. peptide mimicking its loop I (Oncotag) in a xenograft mice model of epidermoid carcinoma. SLURP-1 inhibited the mitogenic pathways and transcription factors in A431 cells, and its antiproliferative activity depended on α7-nAChR. Intravenous treatment of mice with SLURP-1 or Oncotag for 10 days suppressed the tumor growth and metastasis and induced sustained changes in gene and microRNA expression in the tumors. Both SLURP-1 and Oncotag demonstrated no acute toxicity. Surprisingly, Oncotag led to a longer suppression of pro-oncogenic signaling and downregulated expression of pro-oncogenic miR-221 and upregulated expression of KLF4 protein responsible for control of cell differentiation. Affinity purification revealed SLURP-1 interactions with both α7-nAChR and EGFR and selective Oncotag interaction with α7-nAChR. Thus, the selective inhibition of α7-nAChRs by drugs based on Oncotag may be a promising strategy for cancer therapy.
Keywords
