Intrinsic and Extrinsic Control of Hepatocellular Carcinoma by TAM Receptors

Hepatocellular carcinoma (HCC) is the major subtype of liver cancer, showing high mortality of patients due to limited therapeutic options at advanced stages of disease. The receptor tyrosine kinases Tyro3, Axl and MerTK—belonging to the TAM family—exert a large impact on various aspects of cancer b...

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Autores principales:	Viola Hedrich, Kristina Breitenecker, Leila Djerlek, Gregor Ortmayr, Wolfgang Mikulits
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	hepatocellular carcinoma receptor tyrosine kinase TAM Tyro3 Axl MerTK Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/696c343d9b514787af01d0ce532a0c09
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spelling	oai:doaj.org-article:696c343d9b514787af01d0ce532a0c092021-11-11T15:33:17ZIntrinsic and Extrinsic Control of Hepatocellular Carcinoma by TAM Receptors10.3390/cancers132154482072-6694https://doaj.org/article/696c343d9b514787af01d0ce532a0c092021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5448https://doaj.org/toc/2072-6694Hepatocellular carcinoma (HCC) is the major subtype of liver cancer, showing high mortality of patients due to limited therapeutic options at advanced stages of disease. The receptor tyrosine kinases Tyro3, Axl and MerTK—belonging to the TAM family—exert a large impact on various aspects of cancer biology. Binding of the ligands Gas6 or Protein S activates TAM receptors causing homophilic dimerization and heterophilic interactions with other receptors to modulate effector functions. In this context, TAM receptors are major regulators of anti-inflammatory responses and vessel integrity, including platelet aggregation as well as resistance to chemotherapy. In this review, we discuss the relevance of TAM receptors in the intrinsic control of HCC progression by modulating epithelial cell plasticity and by promoting metastatic traits of neoplastic hepatocytes. Depending on different etiologies of HCC, we further describe the overt role of TAM receptors in the extrinsic control of HCC progression by focusing on immune cell infiltration and fibrogenesis. Additionally, we assess TAM receptor functions in the chemoresistance against clinically used tyrosine kinase inhibitors and immune checkpoint blockade in HCC progression. We finally address the question of whether inhibition of TAM receptors can be envisaged for novel therapeutic strategies in HCC.Viola HedrichKristina BreiteneckerLeila DjerlekGregor OrtmayrWolfgang MikulitsMDPI AGarticlehepatocellular carcinomareceptor tyrosine kinaseTAMTyro3AxlMerTKNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5448, p 5448 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hepatocellular carcinoma receptor tyrosine kinase TAM Tyro3 Axl MerTK Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	hepatocellular carcinoma receptor tyrosine kinase TAM Tyro3 Axl MerTK Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Viola Hedrich Kristina Breitenecker Leila Djerlek Gregor Ortmayr Wolfgang Mikulits Intrinsic and Extrinsic Control of Hepatocellular Carcinoma by TAM Receptors
description	Hepatocellular carcinoma (HCC) is the major subtype of liver cancer, showing high mortality of patients due to limited therapeutic options at advanced stages of disease. The receptor tyrosine kinases Tyro3, Axl and MerTK—belonging to the TAM family—exert a large impact on various aspects of cancer biology. Binding of the ligands Gas6 or Protein S activates TAM receptors causing homophilic dimerization and heterophilic interactions with other receptors to modulate effector functions. In this context, TAM receptors are major regulators of anti-inflammatory responses and vessel integrity, including platelet aggregation as well as resistance to chemotherapy. In this review, we discuss the relevance of TAM receptors in the intrinsic control of HCC progression by modulating epithelial cell plasticity and by promoting metastatic traits of neoplastic hepatocytes. Depending on different etiologies of HCC, we further describe the overt role of TAM receptors in the extrinsic control of HCC progression by focusing on immune cell infiltration and fibrogenesis. Additionally, we assess TAM receptor functions in the chemoresistance against clinically used tyrosine kinase inhibitors and immune checkpoint blockade in HCC progression. We finally address the question of whether inhibition of TAM receptors can be envisaged for novel therapeutic strategies in HCC.
format	article
author	Viola Hedrich Kristina Breitenecker Leila Djerlek Gregor Ortmayr Wolfgang Mikulits
author_facet	Viola Hedrich Kristina Breitenecker Leila Djerlek Gregor Ortmayr Wolfgang Mikulits
author_sort	Viola Hedrich
title	Intrinsic and Extrinsic Control of Hepatocellular Carcinoma by TAM Receptors
title_short	Intrinsic and Extrinsic Control of Hepatocellular Carcinoma by TAM Receptors
title_full	Intrinsic and Extrinsic Control of Hepatocellular Carcinoma by TAM Receptors
title_fullStr	Intrinsic and Extrinsic Control of Hepatocellular Carcinoma by TAM Receptors
title_full_unstemmed	Intrinsic and Extrinsic Control of Hepatocellular Carcinoma by TAM Receptors
title_sort	intrinsic and extrinsic control of hepatocellular carcinoma by tam receptors
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/696c343d9b514787af01d0ce532a0c09
work_keys_str_mv	AT violahedrich intrinsicandextrinsiccontrolofhepatocellularcarcinomabytamreceptors AT kristinabreitenecker intrinsicandextrinsiccontrolofhepatocellularcarcinomabytamreceptors AT leiladjerlek intrinsicandextrinsiccontrolofhepatocellularcarcinomabytamreceptors AT gregorortmayr intrinsicandextrinsiccontrolofhepatocellularcarcinomabytamreceptors AT wolfgangmikulits intrinsicandextrinsiccontrolofhepatocellularcarcinomabytamreceptors
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Intrinsic and Extrinsic Control of Hepatocellular Carcinoma by TAM Receptors

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