GANT61 and Lithium Chloride Inhibit the Growth of Head and Neck Cancer Cell Lines Through the Regulation of GLI3 Processing by GSK3beta

Zubčić, Vedran; Rinčić, Nikolina; Kurtović, Matea; Trnski, Diana; Musani, Vesna; Ozretić, Petar; Levanat, Sonja; Leović, Dinko; Sabol, Maja (2020) GANT61 and Lithium Chloride Inhibit the Growth of Head and Neck Cancer Cell Lines Through the Regulation of GLI3 Processing by GSK3beta. International journal of molecular sciences, 21 (17). ISSN 1422-0067

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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 a ecting di erent 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 e ector 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 GSK3 . LiCl treatment increases the inhibitory Ser9 phosphorylation of the GSK3 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.

Item Type:	Article
Uncontrolled Keywords:	hedgehog signaling ; head and neck cancer ; GLI ; GANT61 ; LiCl ; GSK3beta
Subjects:	NATURAL SCIENCES > Biology
Divisions:	Division of Molecular Medicine
Projects:	Project title Project leader Project code Project type Novi molekularni mehanizmi kao mete ciljanih terapija: Interakcije molekula mikroRNA i signalnog puta Hedgehog-GLI u seroznom karcinomu jajnika-MIRnaGLI Sonja Levanat IP-2016-06-1268 HRZZ Regulacija GLI koda u tumorima ovisnim o BRAF/NRAS mutacijama-GLIcode Maja Sabol IP-2018-01-4889 HRZZ
Depositing User:	Sonja Levanat
Date Deposited:	16 Nov 2020 10:11
URI:	http://fulir.irb.hr/id/eprint/6006
DOI:	10.3390/ijms21176410

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