The role of Wnt and Shh signaling systems in noggin-induced tumorigenesis
- Authors: Mardaryev A.N.1, Mardaryev N.S.2, Mardaryeva N.V.3, Schiptsova N.V.3
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Affiliations:
- University of Bradford
- Kazan State Medical University
- Chuvash State Agrarian University
- Issue: Vol 19, No 1 (2024): Factors of sustainable animal productivity: from genomics to therapy
- Pages: 165-175
- Section: Veterinary science
- URL: https://journals.rcsi.science/2312-797X/article/view/315837
- DOI: https://doi.org/10.22363/2312-797X-2024-19-1-165-175
- EDN: https://elibrary.ru/AYIMKC
- ID: 315837
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Abstract
The cross-interaction between BMP, Wnt and Shh signalling pathways in developing epithelial skin tumours remains poorly understood. To study the role of Wnt and Shh signalling pathways in tumour development upon BMP inhibition, we utilized a transgenic mouse model, overexpressing BMP antagonist noggin in the skin epithelium and leading to the development of hair follicle-derived tumours shortly after birth. Comparative gene and protein expression analyses revealed up-regulation of Wnt and Shh signalling systems in the skin of transgenic mice at various stages of follicular tumour development. Furthermore, recombinant BMP-4 suppresses the expression of Shh in the culture of tumor cells, while pharmacological inhibitors of Wnt and Shh significantly slow down the formation and development of tumors in noggin-expressing transgenic mice. These results enhance our knowledge about the role of growth factors in carcinogenesis and may lead to finding new targets for specific therapies for oncological diseases.
Keywords
About the authors
Andrei N. Mardaryev
University of Bradford
Email: A.Mardaryev@bradford.ac.uk
ORCID iD: 0000-0002-7826-5506
SPIN-code: 2645-6478
PhD, Associate Professor, Centre for Sckin Sciences
Richmond Road, Bradford, West Yorkshire, BD7 1DP, United KingdomNikita S. Mardaryev
Kazan State Medical University
Email: nikitamardarjev@yandex.ru
ORCID iD: 0009-0006-3723-2616
SPIN-code: 8791-1497
student
49 Butlerova st., Kazan, Republic of Tatarstan, 420012, Russian FederationNataliya V. Mardaryeva
Chuvash State Agrarian University
Author for correspondence.
Email: volga480@yandex.ru
ORCID iD: 0000-0001-7863-7245
SPIN-code: 5663-0732
Candidate of Biological Sciences, Associate Professor, Head of the Department of Biotechnology and Processing of Agricultural Products
29 Karla Marksa st., Cheboksary, Chuvash Republic, 428003, Russian FederationNadezda V. Schiptsova
Chuvash State Agrarian University
Email: shipnavars@mail.ru
ORCID iD: 0000-0002-7575-6297
SPIN-code: 4486-9698
Candidate of Biological Sciences, Associate Professor
29 Karla Marksa st., Cheboksary, Chuvash Republic, 428003, Russian FederationReferences
- Carreira ACO, Zambuzzi WF, Rossi MC, Astorino Filho R, Sogayar MC, Granjeiro JM. Bone morphogenetic proteins: promising molecules for bone healing, bioengineering, and regenerative medicine. Vitamins & Hormones. 2015;99:293–322. doi: 10.1016/bs.vh.2015.06.002
- Zhou XP, Woodford-Richens K, Lehtonen R, Kurose K, Aldred M, Hampel H, et al. Germline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile polyposis syndrome and of Cowden and Bannayan-Riley-Ruvalcaba syndromes. Am J Hum Genet. 2001;69:704–711.
- Sun L. Tumor-suppressive and promoting function of transforming growth factor beta. Frontiers in Bioscience. 2004;9:1925–1935.
- Hsu MY, Rovinsky S, Penmatcha S, Herlyn M, Muirhead D. Bone morphogenetic proteins in melanoma: angel or devil? Cancer and Metastasis Reviews. 2005;24:251–263. doi: 10.1007/s10555‑005‑1575‑y
- Fuchs E. Scratching the surface of skin development. Nature. 2007;445:834–842. doi: 10.1038/nature05659
- Gat U, DasGupta R, Degenstein L, Fuchs E. De Novo hair follicle morphogenesis and hair tumors in mice expressing a truncated beta-catenin in skin. Cell. 1998;95(5):605–614. doi: 10.1016/S0092‑8674(00)81631‑1
- Grachtchouk M, Mo R, Yu S, Zhang X, Sasaki H, Hui C, et al. Basal cell carcinomas in mice over expressing Gli2 in skin. Nature Genetics. 2000;24:216–217. doi: 10.1038/73417
- Hutchin ME, Kariapper MST, Grachtchouk M, Wang A, Wei L, Cummings D, et al. Sustained Hedgehog signaling is required for basal cell carcinoma proliferation and survival: conditional skin tumorigenesis recapitulates the hair growth cycle. Genes Dev. 2005;19:214–223. doi: 10.1101/gad.1258705
- Niemann C, Owens DM, Hulsken J, Birchmeier W, Watt FM. Expression of ΔNLef1 in mouse epidermis results in differentiation of hair follicles into squamous epidermal cysts and formation of skin tumors. Development. 2003;129(1):95–109. doi: 10.1242/dev.129.1.95
- Oro AE, Higgins KM, Hu Z, Bonifas JM, Epstein EHJ, Scott MP. Basal cell carcinomas in mice overexpressing sonic hedgehog. Science. 1997;276:817–821. doi: 10.1126/science.276.5313.817
- Yang Z, Ellis T, Markant S, Read T, Kessler J, Bourboulas M, et al. Medulloblastoma can be initiated by deletion of Patched in lineage-restricted progenitors or stem cells. Cancer Cell. 2008;14:135–145. doi: 10.1016/j.ccr.2008.07.003
- Mardaryev AN, Mardaryeva NV. The role of cbx4 in regulation of wound healing in mice. In: Scientific-educational environment as a basis for the development of agroindustrial complex social infrastructure of the village: conference proceedings. Cheboksary; 2016. p.305–310.
- Mardaryev AN, Mardaryeva NV, Larionov GА. The role of Cbx7 in regulation of keratinocyte migration during wound healing in mice. Vestnik Chuvash SAU. 2017;(3):56–62.
- Mardaryev AN, Mardaryeva NV. Polycomb protein Cbx7 controls proliferation of keratinocytes in mouse skin. In: Biologization of agriculture — the basis of reproduction of soil fertility: conference proceedings. Cheboksary; 2018. p.171–178.
- Mardaryev AN, Mardaryeva NV, Larionov GA, Gordova VS. Dynamics of Cbx7 Expression in the Epidermis after Wounding of the Skin. Russian journal of physiology. 2019;105(4):456–464. doi: 10.1134/S0869813919040034
- Mardaryev AN, Mardaryeva NV, Larionov GA. BMP of signaling path in the development of skin tumors. Vestnik of Ulyanovsk state agricultural academy. 2019;(1):57–61. doi: 10.18286/1816‑4501‑2019‑1‑57‑61
- Mardaryev AN, Mardaryeva NV. The identification of molecular mechanisms of involvement of BMP in the development of skin tumors. In: Scientific educational and applied aspects of production and processing of agricultural products: conference proceedings. Cheboksary; 2018. p.313–320.
- Sharov AA, Sharova TY, Mardaryev AN, Tommasi di Vignano A, Atoyan R, et al. Bone morphogenetic protein signaling regulates the size of hair follicles and modulates the expression of cell cycle-associated genes. PNAS. 2006;103(48):18166–18171. doi: 10.1073/pnas.060889910
- Tucker AS, Headon DJ, Courtney JM, Overbeek P, Sharpe PT. The activation level of the TNF family receptor, Edar, determines cusp number and tooth number during tooth development. Dev Biol. 2004;268:185–194. doi: 10.1016/j.ydbio.2003.12.019
- Van Mater D, Kolligs F, Dlugosz A, Fearon E. Transient activation of beta-catenin signaling in cutaneous keratinocytes is sufficient to trigger the active growth phase of the hair cycle in mice. Genes Dev. 2003;17:1219–1224. doi: 10.1101/gad.1076103.
- Katoh M. Networking of WNT, FGF, Notch, BMP, and Hedgehog signaling pathways during carcinogenesis. Stem Cell Rev. 2007;3:30–38. doi: 10.1007/s12015‑007‑0006‑6
- Athar M, Tang X, Lee JL, Kopelovich L, Kim AL. Hedgehog signaling in skin development and cancer. Exp Dermatol. 2006;15(9):667–677. doi: 10.1111/j.1600‑0625.2006.00473.x
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