Functional and genetic deconstruction of the cellular origin in liver cancer

Jens U. Marquardt; Jesper B. Andersen; Snorri S. Thorgeirsson

doi:10.1038/nrc4017

Functional and genetic deconstruction of the cellular origin in liver cancer

Jens U. Marquardt, Jesper B. Andersen, Snorri S. Thorgeirsson^*

^*Corresponding author for this work

Clinic of Internal Medicine I

273 Citations (Scopus)

Abstract

During the past decade, research on primary liver cancers has particularly highlighted the uncommon plasticity of differentiated parenchymal liver cells (that is, hepatocytes and cholangiocytes (also known as biliary epithelial cells)), the role of liver progenitor cells in malignant transformation, the importance of the tumour microenvironment and the molecular complexity of liver tumours. Whereas other reviews have focused on the landscape of genetic alterations that promote development and progression of primary liver cancers and the role of the tumour microenvironment, the crucial importance of the cellular origin of liver cancer has been much less explored. Therefore, in this Review, we emphasize the importance and complexity of the cellular origin in tumour initiation and progression, and attempt to integrate this aspect with recent discoveries in tumour genomics and the contribution of the disrupted hepatic microenvironment to liver carcinogenesis.

Original language	English
Journal	Nature Reviews Cancer
Volume	15
Issue number	11
Pages (from-to)	653-667
Number of pages	15
ISSN	1474-175X
DOIs	https://doi.org/10.1038/nrc4017
Publication status	Published - 23.10.2015

Funding

This project was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA (to S.S.T.). J.U.M. is sup‑ ported by grants from the German Research Foundation (MA 4443/2‑1), German Cancer Aid (DKH 110989) and the Volkswagen Foundation (Lichtenberg program). J.B.A. is sup‑ ported by grants from the Danish Cancer Society (Knæk can‑ cer program), the Novo Nordisk Foundation (Hallas‑Møller fellowship), the Danish Medical Research Council (Sapere Aude program) and the A.P. Møller Foundation.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/nrc4017

Cite this

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title = "Functional and genetic deconstruction of the cellular origin in liver cancer",

abstract = "During the past decade, research on primary liver cancers has particularly highlighted the uncommon plasticity of differentiated parenchymal liver cells (that is, hepatocytes and cholangiocytes (also known as biliary epithelial cells)), the role of liver progenitor cells in malignant transformation, the importance of the tumour microenvironment and the molecular complexity of liver tumours. Whereas other reviews have focused on the landscape of genetic alterations that promote development and progression of primary liver cancers and the role of the tumour microenvironment, the crucial importance of the cellular origin of liver cancer has been much less explored. Therefore, in this Review, we emphasize the importance and complexity of the cellular origin in tumour initiation and progression, and attempt to integrate this aspect with recent discoveries in tumour genomics and the contribution of the disrupted hepatic microenvironment to liver carcinogenesis.",

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N2 - During the past decade, research on primary liver cancers has particularly highlighted the uncommon plasticity of differentiated parenchymal liver cells (that is, hepatocytes and cholangiocytes (also known as biliary epithelial cells)), the role of liver progenitor cells in malignant transformation, the importance of the tumour microenvironment and the molecular complexity of liver tumours. Whereas other reviews have focused on the landscape of genetic alterations that promote development and progression of primary liver cancers and the role of the tumour microenvironment, the crucial importance of the cellular origin of liver cancer has been much less explored. Therefore, in this Review, we emphasize the importance and complexity of the cellular origin in tumour initiation and progression, and attempt to integrate this aspect with recent discoveries in tumour genomics and the contribution of the disrupted hepatic microenvironment to liver carcinogenesis.

AB - During the past decade, research on primary liver cancers has particularly highlighted the uncommon plasticity of differentiated parenchymal liver cells (that is, hepatocytes and cholangiocytes (also known as biliary epithelial cells)), the role of liver progenitor cells in malignant transformation, the importance of the tumour microenvironment and the molecular complexity of liver tumours. Whereas other reviews have focused on the landscape of genetic alterations that promote development and progression of primary liver cancers and the role of the tumour microenvironment, the crucial importance of the cellular origin of liver cancer has been much less explored. Therefore, in this Review, we emphasize the importance and complexity of the cellular origin in tumour initiation and progression, and attempt to integrate this aspect with recent discoveries in tumour genomics and the contribution of the disrupted hepatic microenvironment to liver carcinogenesis.

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Functional and genetic deconstruction of the cellular origin in liver cancer

Abstract

Funding

UN SDGs

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Dissecting the heterogeneity of tumor-initiating cells in hepatobiliary cancers: molecular characterization and targeting of stemness features

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Functional and genetic deconstruction of the cellular origin in liver cancer

Abstract

Funding

UN SDGs

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Other files and links

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Projects

Dissecting the heterogeneity of tumor-initiating cells in hepatobiliary cancers: molecular characterization and targeting of stemness features

Cite this