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The Role of Cancer-Associated Fibroblasts and Fibrosis in Liver Cancer
Open accessAbstract
Liver cancer is the second leading cause of cancer mortality worldwide, causing more than 700,000 deaths annually. Because of the wide landscape of genomic alterations and limited therapeutic success of targeting tumor cells, a recent focus has been on better understanding and possibly targeting the microenvironment in which liver tumors develop. A unique feature of liver cancer is its close association with liver fibrosis. More than 80% of hepatocellular carcinomas (HCCs) develop in fibrotic or cirrhotic livers, suggesting an important role of liver fibrosis in the premalignant environment (PME) of the liver. Cholangiocarcinoma (CCA), in contrast, is characterized by a strong desmoplasia that typically occurs in response to the tumor, suggesting a key role of cancer-associated fibroblasts (CAFs) and fibrosis in its tumor microenvironment (TME). Here, we discuss the functional contributions of myofibroblasts, CAFs, and fibrosis to the development of HCC and CCA in the hepatic PME and TME, focusing on myofibroblast- and extracellular matrix–associated growth factors, fibrosis-associated immunosuppressive pathways, as well as mechanosensitive signaling cascades that are activated by increased tissue stiffness. Better understanding of the role of myofibroblasts in HCC and CCA development and progression may provide the basis to target these cells for tumor prevention or therapy.
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“Normal liver tissue has been reported to have an elastic modulus around several kilo Pascal, whereas fibrosis causes increased tissue rigidity to up to 20 kPa (Fig. 5L) (31, 32).”
From Stiffness sensing via Piezo1 enhances macrophage efferocytosis and promotes the resolution of liver fibrosis (2024) · cites this paper as [31]
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“Notably, there is a strong correlation between hepatic fibrosis and HCC development with 80–90% of HCCs developing in fibrotic or cirrhotic livers.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [70]
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“Moreover, this antibiotic cocktail also reduced liver fibrosis 73, which often precedes HCC and represents a risk factor for HCC development in CLD70.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [70]
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Self-citation
Metadata
- Authors
- Affo, S., Yu, L.-X., & Schwabe, R. F.
- Affiliations
- Department of Medicine, Columbia University, New York, NY 10032;
- Columbia University (US)
- Venue
- Annual Review of Pathology: Mechanisms of Disease
- Publisher
- Annual Reviews
- Published
- 2017-01-24
- Volume
- 12
- Issue
- 1
- Pages
- 153-186
- ISSN
- 1553-4006 (ISSN-L)
- 1553-4014
- PMC
- PMC5720358
- OpenAlex
- W2411225414
- Cited by
- 757
- References
- 269
- Citations by year
- 2026: 62 · 2025: 97 · 2024: 96 · 2023: 107 · 2022: 104 · 2021: 94 · 2020: 101 · 2019: 48 · 2018: 36 · 2017: 12
- FWCI
- 3.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Annual Review of Pathology Mechanisms of Disease (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA190844, R01CA200597)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
- Keywords
- cancer-associated fibroblasts, liver fibrosis, hepatocellular carcinoma, cholangiocarcinoma, tumor microenvironment, myofibroblasts, desmoplasia, extracellular matrix, growth factors, immunosuppression, mechanosensitive signaling, tissue stiffness, liver cirrhosis, liver cancer progression
- MeSH terms
- Cancer-Associated Fibroblasts, Animals, Humans, Liver Cirrhosis, Liver Neoplasms, Signal Transduction, Myofibroblasts, Tumor Microenvironment
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