GANT61 and Lithium Chloride Inhibit the Growth of Head and Neck Cancer Cell Lines Through the Regulation of GLI3 Processing by GSK3β

Zubčić, Vedran; Rinčić, Nikolina; Kurtović, Matea; Trnski, Diana; Musani, Vesna; Ozretić, Petar; Levanat, Sonja; Leović, Dinko; Sabol, Maja

doi:10.3390/ijms21176410

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GANT61 and Lithium Chloride Inhibit the Growth of Head and Neck Cancer Cell Lines Through the Regulation of GLI3 Processing by GSK3β

^1,2,†,

^3,†,

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Department of Maxillofacial Surgery, University Hospital Osijek, Ulica Josipa Huttlera 4, Osijek 31000, Croatia

School of Medicine, The Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, Osijek 31000, Croatia

Laboratory for Hereditary Cancer, Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, Zagreb 10000, Croatia

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Department of Otorhinolaryngology and Head and Neck Surgery, Maxillofacial Surgery Unit, Clinical Hospital Centre Zagreb, Kišpatićeva ulica 12, Zagreb 10000, Croatia

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2020, 21(17), 6410; https://doi.org/10.3390/ijms21176410

Received: 11 August 2020 / Revised: 28 August 2020 / Accepted: 1 September 2020 / Published: 3 September 2020

(This article belongs to the Special Issue Hedgehog Signaling 2.0)

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Abstract

Several signaling pathways are aberrantly activated in head and neck squamous cell carcinoma (HNSCC), including the Hedgehog-Gli (HH-GLI), WNT, EGFR, and NOTCH pathways. The HH-GLI pathway has mostly been investigated in the context of canonical signal transduction and the inhibition of the membrane components of the pathway. In this work we investigated the role of downstream inhibitors GANT61 and lithium chloride (LiCl) on cell viability, wound closure, and colony forming ability of HNSCC cell lines. Five HNSCC cell lines were treated with HH-GLI pathway inhibitors affecting different levels of signal transduction. GANT61 and LiCl reduce the proliferation and colony formation capabilities of HNSCC cell lines, and LiCl has an additional effect on wound closure. The major effector of the HH-GLI signaling pathway in HNSCC is the GLI3 protein, which is expressed in its full-length form and is functionally regulated by GSK3β. LiCl treatment increases the inhibitory Ser9 phosphorylation of the GSK3β protein, leading to increased processing of GLI3 from full-length to repressor form, thus inhibiting HH-GLI pathway activity. Therefore, downstream inhibition of HH-GLI signaling may be a promising therapeutic strategy for HNSCC. View Full-Text

Keywords: hedgehog signaling; head and neck cancer; GLI; GANT61; LiCl; GSK3β

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Zubčić, V.; Rinčić, N.; Kurtović, M.; Trnski, D.; Musani, V.; Ozretić, P.; Levanat, S.; Leović, D.; Sabol, M. GANT61 and Lithium Chloride Inhibit the Growth of Head and Neck Cancer Cell Lines Through the Regulation of GLI3 Processing by GSK3β. Int. J. Mol. Sci. 2020, 21, 6410. https://doi.org/10.3390/ijms21176410

AMA Style

Zubčić V, Rinčić N, Kurtović M, Trnski D, Musani V, Ozretić P, Levanat S, Leović D, Sabol M. GANT61 and Lithium Chloride Inhibit the Growth of Head and Neck Cancer Cell Lines Through the Regulation of GLI3 Processing by GSK3β. International Journal of Molecular Sciences. 2020; 21(17):6410. https://doi.org/10.3390/ijms21176410

Chicago/Turabian Style

Zubčić, Vedran, Nikolina Rinčić, Matea Kurtović, Diana Trnski, Vesna Musani, Petar Ozretić, Sonja Levanat, Dinko Leović, and Maja Sabol. 2020. "GANT61 and Lithium Chloride Inhibit the Growth of Head and Neck Cancer Cell Lines Through the Regulation of GLI3 Processing by GSK3β" International Journal of Molecular Sciences 21, no. 17: 6410. https://doi.org/10.3390/ijms21176410

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GANT61 and Lithium Chloride Inhibit the Growth of Head and Neck Cancer Cell Lines Through the Regulation of GLI3 Processing by GSK3β

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