Cellular Origin of Hepatocellular Carcinoma

Schneller, Doris; Angel, Peter

doi:10.15586/hepatocellularcarcinoma.2019.ch1

Cited by 7 publications

(8 citation statements)

References 171 publications

(196 reference statements)

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“…The cellular compartment giving rise to the tumor-initiating cell in HCC is under intense debate, and either progenitor/stem cells or differentiated liver cells could be responsible. Experimental evidence indicates a model where every cell can be a key player [123]. There is profound inter-tumoral heterogeneity in HCC with respect to genetic profiles, allowing for the discrimination of at least two genetic/molecular subgroups, as described above [7,124], and transcriptional profiling can distinguish different prognostic subgroups.…”

Section: Stem Cells In the Normal Livermentioning

confidence: 99%

The Cancer Stem Cell in Hepatocellular Carcinoma

Schulte

López-Gil

Sáinz

et al. 2020

Cancers

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The recognition of intra-tumoral cellular heterogeneity has given way to the concept of the cancer stem cell (CSC). According to this concept, CSCs are able to self-renew and differentiate into all of the cancer cell lineages present within the tumor, placing the CSC at the top of a hierarchical tree. The observation that these cells—in contrast to bulk tumor cells—are able to exclusively initiate new tumors, initiate metastatic spread and resist chemotherapy implies that CSCs are solely responsible for tumor recurrence and should be therapeutically targeted. Toward this end, dissecting and understanding the biology of CSCs should translate into new clinical therapeutic approaches. In this article, we review the CSC concept in cancer, with a special focus on hepatocellular carcinoma.

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Section: Stem Cells In the Normal Livermentioning

confidence: 99%

The Cancer Stem Cell in Hepatocellular Carcinoma

Schulte

López-Gil

Sáinz

et al. 2020

Cancers

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“…The functional LCSC marker CD24 was found to drive liver CSC genesis through STAT3-mediated Nanog regulation (Lee et al, 2011). The IL-6/STAT3 signaling pathway was proposed to be related to liver inflammation and liver regeneration (Schneller and Angel, 2019), and the mechanism is to maintain the liver CSC population through interaction with the TGF-β signaling pathway (Tang et al, 2008). A recent study demonstrated that the IL6/STAT3 signaling cascade mainly causes CD133 + enrichment in liver cancer (Won et al, 2015).…”

Section: Stat3 Signalingmentioning

confidence: 99%

Emerging Regulatory Mechanisms Involved in Liver Cancer Stem Cell Properties in Hepatocellular Carcinoma

Chen

et al. 2021

Front. Cell Dev. Biol.

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Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer and one of the leading causes of cancer-related deaths worldwide. A growing body of evidence supports the hypothesis that HCC is driven by a population of cells called liver cancer stem cells (LCSCs). LCSCs have been proposed to contribute to malignant HCC progression, including promoting tumor occurrence and growth, mediating tumor metastasis, and treatment resistance, but the regulatory mechanism of LCSCs in HCC remains unclear. Understanding the signaling pathways responsible for LCSC maintenance and survival may provide opportunities to improve patient outcomes. Here, we review the current literature about the origin of LCSCs and the niche composition, describe the current evidence of signaling pathways that mediate LCSC stemness, then highlight several mechanisms that modulate LCSC properties in HCC progression, and finally, summarize the new developments in therapeutic strategies targeting LCSCs markers and regulatory pathways.

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“…Among these were 0.84 million new liver cancer patients and 0.78 million new deaths due to liver cancer. An analysis of 38 specific cancers detailed in GLOBOCAN 2018 revealed that liver cancer is the third most fatal cancer, 1 and hepatocellular carcinoma (HCC) is the main type of liver cancer 2 . Viral HCC is caused by chronic infection with the hepatitis B or hepatitis C virus 2 and was predominant in Western countries and Japan until the late 1990s.…”

Section: Introductionmentioning

confidence: 99%

Circular RNAs hsa_circ_0001438 and hsa_circ_0000417 are downregulated and upregulated, respectively, in hepatocellular carcinoma

Imanishi

Nagata

Fujita

et al. 2022

Int J Experimental Path

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Hepatocellular carcinoma (HCC) is the most predominant type of liver cancer and is frequently fatal. Alpha‐fetoprotein, alpha‐fetoprotein‐L3, and protein induced by vitamin K absence or antagonist‐II are used as biomarkers to diagnose HCC. However, these biomarkers are not highly specific, especially for early‐stage HCC diagnosis; therefore, more specific biomarkers are needed. Recently, circular RNA (circRNA) biomarkers have been used to diagnose several intractable diseases. In this study, we sought to identify circRNA biomarkers for the specific diagnosis of HCC. To this end, we compared the expression levels of circRNAs in primary HCC and normal tissues using publicly available RNA‐seq data. Our analysis revealed that the expression levels of eight circRNAs were altered in primary HCC tissues compared with normal tissues. To confirm our findings, we examined the expression levels of selected circRNAs in HCC cell lines and normal hepatocytes. The expression level of hsa_circ_0001438, a circRNA that was downregulated in primary HCC, was lower in poorly and well‐differentiated HCC cell lines than in normal hepatocytes. By contrast, the expression level of hsa_circ_0000417, which was increased in primary HCC, was strongly upregulated in a well‐differentiated HCC cell line compared with normal hepatocytes. Thus, hsa_circ_0001438 and hsa_circ_0000417 might be potential biomarkers for the specific diagnosis of HCC. The experimental strategy described here, using publicly available RNA‐seq data, is a useful and cost‐effective method of identifying circRNA biomarkers.

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Cellular Origin of Hepatocellular Carcinoma

Cited by 7 publications

References 171 publications

The Cancer Stem Cell in Hepatocellular Carcinoma

The Cancer Stem Cell in Hepatocellular Carcinoma

Emerging Regulatory Mechanisms Involved in Liver Cancer Stem Cell Properties in Hepatocellular Carcinoma

Circular RNAs hsa_circ_0001438 and hsa_circ_0000417 are downregulated and upregulated, respectively, in hepatocellular carcinoma

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