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

A431 Ly6/uPAR SLURP-1 cancer lynx1 xenograft α7-nAChR

Journal

Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250

Informations de publication

Date de publication:
2023
Historique:
received: 11 07 2023
accepted: 19 09 2023
medline: 19 10 2023
pubmed: 19 10 2023
entrez: 19 10 2023
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.3389/fcell.2023.1256716 PMID: 37854069 PMC: PMC10580074
pubmed: 37854069
doi: 10.3389/fcell.2023.1256716
pii: 1256716
pmc: PMC10580074
doi:

Types de publication

Journal Article

Langues

eng

Pagination

1256716

Informations de copyright

Copyright © 2023 Shlepova, Shulepko, Shipunova, Bychkov, Kukushkin, Chulina, Azev, Shramova, Kazakov, Ismailova, Palikova, Palikov, Kalabina, Shaykhutdinova, Slashcheva, Tukhovskaya, Dyachenko, Murashev, Deyev, Kirpichnikov, Shenkarev and Lyukmanova.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

O V Shlepova (OV)

NTI Center, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Moscow Institute of Physics and Technology, National Research University, Dolgoprudny, Russia.

M A Shulepko (MA)

Faculty of Biology, Shenzhen MSU-BIT University, Shenzhen, China.

V O Shipunova (VO)

Moscow Institute of Physics and Technology, National Research University, Dolgoprudny, Russia.
Immunology Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.

M L Bychkov (ML)

NTI Center, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.

I D Kukushkin (ID)

Moscow Institute of Physics and Technology, National Research University, Dolgoprudny, Russia.
Bioengineering Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.

I A Chulina (IA)

Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia.

V N Azev (VN)

Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia.

E I Shramova (EI)

Immunology Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.

V A Kazakov (VA)

Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia.

A M Ismailova (AM)

Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia.

Y A Palikova (YA)

Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia.

V A Palikov (VA)

Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia.

E A Kalabina (EA)

Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia.

E A Shaykhutdinova (EA)

Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia.

G A Slashcheva (GA)

Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia.

E A Tukhovskaya (EA)

Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia.

I A Dyachenko (IA)

Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia.

A N Murashev (AN)

Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Pushchino, Russia.

S M Deyev (SM)

Immunology Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Biomarker Research Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.
Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.

M P Kirpichnikov (MP)

Bioengineering Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
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 (ZO)

NTI Center, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Moscow Institute of Physics and Technology, National Research University, Dolgoprudny, Russia.
Structural Biology Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.

E N Lyukmanova (EN)

Faculty of Biology, Shenzhen MSU-BIT University, Shenzhen, China.
Bioengineering Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
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.

Classifications MeSH