Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) is overexpressed in cholangiocarcinoma and its expression correlates with S100 calcium-binding protein A4 (S100A4)

Cholangiocarcinoma (CCA) is the second most malignant neoplasm in the liver that arises from the biliary tree. CCA is associated with a poor prognosis, and the key players involved in its pathogenesis are still not well understood. Receptor tyrosine kinases (RTKs), such as epidermal growth factor re...

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Autores principales:	Michele A. Rodrigues, Dawidson A. Gomes, Ana Luiza Cosme, Marcelo Dias Sanches, Vivian Resende, Geovanni D. Cassali
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	ITPRs ITPR3 S100A4 Cholangiocarcinoma Liver Cancer Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/4242346583a14d46a6363d7164a7a263
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spelling	oai:doaj.org-article:4242346583a14d46a6363d7164a7a2632021-11-18T04:43:35ZInositol 1,4,5-trisphosphate receptor type 3 (ITPR3) is overexpressed in cholangiocarcinoma and its expression correlates with S100 calcium-binding protein A4 (S100A4)0753-332210.1016/j.biopha.2021.112403https://doaj.org/article/4242346583a14d46a6363d7164a7a2632022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221011896https://doaj.org/toc/0753-3322Cholangiocarcinoma (CCA) is the second most malignant neoplasm in the liver that arises from the biliary tree. CCA is associated with a poor prognosis, and the key players involved in its pathogenesis are still not well understood. Receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor (EGFR), can mediate intracellular calcium (Ca2+) signaling pathways via inositol 1,4,5-trisphosphate (InsP3), activating inositol 1,4,5-trisphosphate receptors (ITPRs) and regulating tumor growth. ITPR isoform 3 (ITPR3) is the main intracellular Ca2+ release channel in cholangiocytes. The effects of intracellular Ca2+ are mediated by calcium-binding proteins such as Calmodulin and S100 calcium-binding protein A4 (S100A4). However, the clinicopathological and biological significance of EGFR, ITPR3 and S100A4 in CCA remains unclear. Thus, the present work investigates the immunoexpression of these three proteins in 59 CCAs from patients who underwent curative surgical treatment and correlates the data with clinicopathological features and survival. High ITPR3 expression was correlated with CA 19-9 levels, TNM stage and lymph node metastasis (N). Furthermore, ITPR3 expression was increased in distal CCA compared to control bile ducts and intrahepatic and perihilar CCAs. These observations were confirmed by proteomic analysis. ITPR3 and S100A4 clinical scores were significantly correlated. Furthermore, it was demonstrated that EGF induces calcium signaling in a cholangiocarcinoma cell line and ITPR3 colocalizes with nonmuscle myosin IIA (NMIIA). In summary, ITPR3 overexpression could contribute to CCA progression and it may represent a potential therapeutic target.Michele A. RodriguesDawidson A. GomesAna Luiza CosmeMarcelo Dias SanchesVivian ResendeGeovanni D. CassaliElsevierarticleITPRsITPR3S100A4CholangiocarcinomaLiverCancerTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 145, Iss , Pp 112403- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	ITPRs ITPR3 S100A4 Cholangiocarcinoma Liver Cancer Therapeutics. Pharmacology RM1-950
spellingShingle	ITPRs ITPR3 S100A4 Cholangiocarcinoma Liver Cancer Therapeutics. Pharmacology RM1-950 Michele A. Rodrigues Dawidson A. Gomes Ana Luiza Cosme Marcelo Dias Sanches Vivian Resende Geovanni D. Cassali Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) is overexpressed in cholangiocarcinoma and its expression correlates with S100 calcium-binding protein A4 (S100A4)
description	Cholangiocarcinoma (CCA) is the second most malignant neoplasm in the liver that arises from the biliary tree. CCA is associated with a poor prognosis, and the key players involved in its pathogenesis are still not well understood. Receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor (EGFR), can mediate intracellular calcium (Ca2+) signaling pathways via inositol 1,4,5-trisphosphate (InsP3), activating inositol 1,4,5-trisphosphate receptors (ITPRs) and regulating tumor growth. ITPR isoform 3 (ITPR3) is the main intracellular Ca2+ release channel in cholangiocytes. The effects of intracellular Ca2+ are mediated by calcium-binding proteins such as Calmodulin and S100 calcium-binding protein A4 (S100A4). However, the clinicopathological and biological significance of EGFR, ITPR3 and S100A4 in CCA remains unclear. Thus, the present work investigates the immunoexpression of these three proteins in 59 CCAs from patients who underwent curative surgical treatment and correlates the data with clinicopathological features and survival. High ITPR3 expression was correlated with CA 19-9 levels, TNM stage and lymph node metastasis (N). Furthermore, ITPR3 expression was increased in distal CCA compared to control bile ducts and intrahepatic and perihilar CCAs. These observations were confirmed by proteomic analysis. ITPR3 and S100A4 clinical scores were significantly correlated. Furthermore, it was demonstrated that EGF induces calcium signaling in a cholangiocarcinoma cell line and ITPR3 colocalizes with nonmuscle myosin IIA (NMIIA). In summary, ITPR3 overexpression could contribute to CCA progression and it may represent a potential therapeutic target.
format	article
author	Michele A. Rodrigues Dawidson A. Gomes Ana Luiza Cosme Marcelo Dias Sanches Vivian Resende Geovanni D. Cassali
author_facet	Michele A. Rodrigues Dawidson A. Gomes Ana Luiza Cosme Marcelo Dias Sanches Vivian Resende Geovanni D. Cassali
author_sort	Michele A. Rodrigues
title	Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) is overexpressed in cholangiocarcinoma and its expression correlates with S100 calcium-binding protein A4 (S100A4)
title_short	Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) is overexpressed in cholangiocarcinoma and its expression correlates with S100 calcium-binding protein A4 (S100A4)
title_full	Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) is overexpressed in cholangiocarcinoma and its expression correlates with S100 calcium-binding protein A4 (S100A4)
title_fullStr	Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) is overexpressed in cholangiocarcinoma and its expression correlates with S100 calcium-binding protein A4 (S100A4)
title_full_unstemmed	Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) is overexpressed in cholangiocarcinoma and its expression correlates with S100 calcium-binding protein A4 (S100A4)
title_sort	inositol 1,4,5-trisphosphate receptor type 3 (itpr3) is overexpressed in cholangiocarcinoma and its expression correlates with s100 calcium-binding protein a4 (s100a4)
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/4242346583a14d46a6363d7164a7a263
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Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) is overexpressed in cholangiocarcinoma and its expression correlates with S100 calcium-binding protein A4 (S100A4)

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