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Mechano-Signaling Aspects of Hepatocellular Carcinoma

Journal

JOURNAL OF CANCER
Volume 12, Issue 21, Pages 6411-6421

Publisher

IVYSPRING INT PUBL
DOI: 10.7150/jca.60102

Keywords

Hepatocellular carcinoma; HCC; mechano-signaling; extracellular matrix; ECM; stiffness

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Funding

  1. German Academic Exchange Service (DAAD)

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Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide, with most cases being associated with chronic liver fibrosis which leads to increased liver tissue stiffness. Changes in tissue stiffness affect mechanical signaling pathways, modulating the progression of HCC-related genes. However, mechanical signaling pathways are still less emphasized in comparison to classical biochemical signaling pathways in our understanding of cancer.
HCC is one of the leading causes of cancer related death worldwide and comprises about 90% of the cases of primary liver cancer. It is generally accompanied by chronic liver fibrosis characterised by deposition of collagen fibres, which, in turn, causes enhanced stiffness of the liver tissue. Changes of tissue stiffness give rise to alterations of signalling pathways that are associated to mechanical properties of the cells and the extracellular matrix, and that can be subsumed as mechano-signaling pathways, like, e.g., the YAP/TAZ pathway, or the SRF pathway. Stiffness of the liver tissue modulates mechanical regulation of many genes involved in HCC progression. However, mechano-signaling is still rather underrepresented in our concepts of cancer in comparison to classical biochemical signalling pathways. This review aims to give an overview of various stiffness induced mechano-biological aspects of HCC.

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