Recent progress in understanding, diagnosing, and treating hepatocellular carcinoma

Maluccio, Mph Mary; Covey, Anne M.

doi:10.3322/caac.21161

Cited by 732 publications

(584 citation statements)

References 43 publications

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“…The majority of HCC cases are caused by chronic hepatitis B or hepatitis C infections (2). HCC, characterized by rapid recurrence and poor survival, remains a challenging disease to treat (3). As HCC is not sensitive to radiotherapy or chemotherapy, surgery is the only effective treatment (4).…”

Section: Introductionmentioning

confidence: 99%

“…As HCC is not sensitive to radiotherapy or chemotherapy, surgery is the only effective treatment (4). However, the rate of recurrence is high and metastasis is common following surgery, which leads to the poor prognosis for HCC (3). Therefore, it is necessary to understand the molecular mechanisms underlying the growth and metastasis of HCC, which may help to identify effective diagnosis and therapeutic targets to improve the survival.…”

Section: Introductionmentioning

confidence: 99%

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R-spondin 2 promotes proliferation and migration via the Wnt/β-catenin pathway in human hepatocellular carcinoma

Yin

Wang

et al. 2017

Oncology Letters

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Abstract. Hepatocellular carcinoma (HCC) is a leading cause of malignant disease-associated mortality, particularly in China. The RSPO2 (R-spondin 2) gene is evolutionarily conserved in vertebrates and is involved in developmental and physiological processes. Importantly, RSPO2 has been reported to be associated with colon cancer and potentiate the Wnt/β-catenin signaling pathway. In the present study, enhanced expression of RSPO2 in HCC was observed using tissue microarray. Similarly, the expression level of RSPO2 was higher in HepG2, Huh7 and Hep3B cells but lower in Bel7404 and QGY7703 cells compared with human normal QSG7701 liver cells. Subsequently, gain-of-function studies indicated that RSPO2 promotes the proliferation and migration of QGY7703 cells based on lentivirus-based gene delivery. Furthermore, it was revealed that p21 and leptin, rather than vascular endothelial growth factor-A, are involved in the function of RSPO2 in QGY7703 cells. Particularly, the signal transducer and activator of transcription 3 (STAT3) and Wnt/β-catenin signaling pathways are involved in this process. Overexpression of RSPO2 resulted in the elevated expression of phosphorylated STAT3, β-catenin and c-Myc. Therefore, the present study is beneficial to the understanding of RSPO2-involved liver cancer transformation and drug discovery.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

R-spondin 2 promotes proliferation and migration via the Wnt/β-catenin pathway in human hepatocellular carcinoma

Yin

Wang

et al. 2017

Oncology Letters

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“…HCC has become one of the most common malignancies in the world (3,4). Although multiple novel diagnostic and therapeutic methods have been developed, HCC remains a fatal disease, and >500,000 patients die from HCC each year (5). Malignancies including HCC have unique biological behaviors, such as metastasis and migration, which usually cause treatment failure and poor prognosis (6).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of CD147 is associated with poor prognosis, tumor cell migration and ERK signaling pathway activation in hepatocellular carcinoma

Xiao

Zhao

Shen

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The aim of the present study was to reveal the prognostic significance of CD147 and to preliminarily explore the molecular mechanisms involved. Blood and tumor tissue specimens were obtained from 133 HCC patients. All patients were followed up for 4 years. The serum and tissue levels of CD147 were analyzed using ELISA and immunohistochemistry, respectively. The SMMC-7721 hepatoma carcinoma cell line was transfected with CD147 overexpression vector and cell migration was evaluated using a wound healing assay. Extracellular signal-regulated kinase (ERK) inhibitor UO126 was applied to study the role of the ERK pathway in cell migration. CD147 expression in HCC tissue was associated with poor prognosis of patients [odds ratio (OR): 3.13, 95% confidence interval (CI): 1.52-6.43], and patients with no CD147 expression had a significantly survival advantage (P=0.016). However, serum CD147 levels had no such prognostic significance (OR: 1.94, 95% CI: 0.96-3.91; P=0.097). In the wound healing assay, the wound distance in the non-transfected cell group was wider than that in the transfected cell group without UO126 treatment (178.0±31.1 vs. 106.0±20.7 µm; P=0.003), but similar to that in the transfected cell group with 10 µM UO126 treatment (170.4±13.2 µm; P=0.629). The present study revealed that the expression of CD147 in HCC tissue is an independent prognostic indicator. In addition CD147 overexpression may be associated with tumor cell migration and ERK signaling pathway activation.

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“…In the situation of liver cancer or hepatocirrhosis, surgical resection is a standard medical therapy. Cirrhosis of the liver is one of the leading causes of mortality, and liver cancer is the third most common cancer and the second leading cause of cancer-associated mortality worldwide (5,6).…”

Section: Introductionmentioning

confidence: 99%

Knockout of krüppel-like factor 10 suppresses hepatic cell proliferation in a partially hepatectomized mouse model

et al. 2017

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Abstract. The liver has marked regenerative capabilities, and numerous signaling pathways are involved in liver regeneration. The transforming growth factor-β (TGF-β)/Smad pathway, which is also involved in liver regeneration, regulates numerous biological processes. Krüppel-like factor 10 (KLF10) has been reported to activate the TGF-β/Smad signaling pathway; however, the exact functions of KLF10 under various pathophysiological conditions remain unclear. In the present study, the role of KLF10 in liver regeneration following partial hepatectomy (PH) was investigated using KLF10-knockout (KO) mice. KLF10-KO mice exhibited lower liver/body weight ratios and 5-bromo-2-deoxy-uridine labeling indices compared with wild-type (WT) mice, and significant differences (P= 0.028) were obtained at 72 h after PH. To understand the causes of the gross and histopathological findings, the expression levels of the components of the TGF-β/Smad pathway were examined using reverse transcription-quantitative polymerase chain reaction and western blot analysis. The mRNA and protein levels of Smad3, p15, TGF-β1 and TGF-β receptor 1 were significantly increased, while those of cMyc and cyclin D1 (proliferation-associated genes) were significantly lower in the liver tissues of the KLF10-KO mice compared with those of the WT mice at 72 h post-PH. These results indicated that KLF10-KO may exhibit antiproliferative effects on liver regeneration following PH, through strengthening the TGF-β/Smad signaling pathway in a delayed manner.

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Recent progress in understanding, diagnosing, and treating hepatocellular carcinoma

Cited by 732 publications

References 43 publications

R-spondin 2 promotes proliferation and migration via the Wnt/β-catenin pathway in human hepatocellular carcinoma

R-spondin 2 promotes proliferation and migration via the Wnt/β-catenin pathway in human hepatocellular carcinoma

Overexpression of CD147 is associated with poor prognosis, tumor cell migration and ERK signaling pathway activation in hepatocellular carcinoma

Knockout of krüppel-like factor 10 suppresses hepatic cell proliferation in a partially hepatectomized mouse model

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