Hepatocellular carcinoma stem cells origins and roles in hepatocarcinogenesis and disease progression

Cao, Deliang

doi:10.2741/e448

Cited by 27 publications

(4 citation statements)

References 106 publications

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“…Cancer stem cells (CSCs) are capable of self-renewal and differentiation into heterogeneous tumor cells, and they have been considered to be responsible for tumor initiation, proliferation, and recurrence [59,60]. Additionally, CSCs are resistant to chemotherapy and radiotherapy and are associated with cancer metastasis [61]. Since CSCs can survive after traditional chemotherapy and result in tumor recurrence and drug resistance [62,63], elimination of CSCs in tumor tissues may become an effective anti-cancer therapeutic strategy.…”

Section: Roles Of C-myc In the Regulation Of Cancer Stem Cell-relamentioning

confidence: 99%

Emerging Roles of C-Myc in Cancer Stem Cell-Related Signaling and Resistance to Cancer Chemotherapy: A Potential Therapeutic Target Against Colorectal Cancer

Elbadawy

Usui

Yamawaki

et al. 2019

IJMS

194

139

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Myc is a nuclear transcription factor that mainly regulates cell growth, cell cycle, metabolism, and survival. Myc family proteins contain c-Myc, n-Myc, and l-Myc. Among them, c-Myc can become a promising therapeutic target molecule in cancer. Cancer stem cells (CSCs) are known to be responsible for the therapeutic resistance. In the previous study, we demonstrated that c-Myc mediates drug resistance of colorectal CSCs using a patient-derived primary three-dimensional (3D) organoid culture. In this review, we mainly focus on the roles of c-Myc-related signaling in the regulation of CSCs, chemotherapy resistance, and colorectal cancer organoids. Finally, we introduce the various types of c-Myc inhibitors and propose the possibility of c-Myc as a therapeutic target against colorectal cancer.

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Section: Roles Of C-myc In the Regulation Of Cancer Stem Cell-relamentioning

confidence: 99%

Emerging Roles of C-Myc in Cancer Stem Cell-Related Signaling and Resistance to Cancer Chemotherapy: A Potential Therapeutic Target Against Colorectal Cancer

Elbadawy

Usui

Yamawaki

et al. 2019

IJMS

194

139

View full text Add to dashboard Cite

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“…Cancer stem cells (CSCs) are considered a major threat to the treatment response and prognosis of various cancers, including colorectal cancer (2,3). They are a group of tumor cells with the characteristics of stem cells: self-renewal, infinite proliferation, and the potential of multi-directional differentiation (2,4).…”

Section: Introductionmentioning

confidence: 99%

“…They are a group of tumor cells with the characteristics of stem cells: self-renewal, infinite proliferation, and the potential of multi-directional differentiation (2,4). Although CSCs account for a very minor population of cancer, they are firmly related to tumor metastasis, drug resistance, and recurrence after primary treatment (3). Colorectal cancer stem cells (CR-CSCs) share the major biological characteristics of stem cells from other solid tumors.…”

Section: Introductionmentioning

confidence: 99%

The Role of KDM2B and EZH2 in Regulating the Stemness in Colorectal Cancer Through the PI3K/AKT Pathway

et al. 2021

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Background: The incidence of colorectal cancer (CRC) has been increasing worldwide in recent years. Targeting cancer stem cells (CSCs) in CRC remains a difficult challenge. KDM2B and EZH2 play important role in the maintenance of CSCs' self-renewal capacity and tumorigenic ability; however, the biological functions of those genes in CRC remain unclear. In this study, we aimed to define the contribution of the expression of KDM2B in the features of CRC and establish the relationship between KDM2B and EZH2 in colorectal CSCs.Methods: The expression of KDM2B and EZH2 in the specimens of CRC and CRC cell lines were analyzed by immunohistochemistry, Western blot, and immunofluorescence. The underlying mechanisms of altered expressions of KDM2B and EZH2 and their impact on the biologic features of CRC and stemness in CRC were investigated.Results: The KDM2B gene was highly expressed in CRC tissues, and its overexpression positively correlated with tumor stages and tumor/node/metastasis (TNM) classification. The downregulation of KDM2B retarded cell proliferation, induced DNA damage, reduced spheroid formation, and decreased CRC stem cell markers: CD44, CD133, and ALDH-1. Moreover, the downregulation of KDM2B decreased the expression of EZH2 and both regulated cell migration, invasion, and stemness in the CRC cell line. Additionally, the interaction between KDM2B and EZH2 significantly increased the components of the PI3K/AKT pathway including AKT and PI3K. The high expression of KDM2B positively correlated with EZH2 in CRC tissues.Conclusion: This study shows that the downregulation of KDM2B and EZH2 can regulate CRC cell stemness, and their interaction may serve as a novel prognostic marker and therapeutic target for patients with CRC.

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“…Previous evidence has suggested that the cytological origin of HCC is derived from the abnormal differentiation of stem or oval cells in the liver ( 8 ). Hepatic oval cells (HOCs) are endogenous stem cells of the liver that can differentiate into liver cells for organ regeneration or transform into liver cancer cells to form malignant tumors ( 9 ). When the liver is severely and permanently damaged and the regeneration ability of mature hepatocytes is inhibited, HOCs proliferate in large quantities, thus replacing hepatocytes to repair liver tissue ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

Kangxianruangan granule‑containing serum mediated inhibition of hepatic oval cell differentiation into hepatocellular carcinoma cells via the Wnt‑1/β‑catenin signaling pathway

et al. 2021

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Hepatocellular carcinoma is a malignancy with poor clinical prognosis. Hepatic oval cells (HOCs) tend to differentiate into cancerous hepatocellular carcinoma cells (HCCs) in the tumor microenvironment. The purpose of the present study was to explore the role of kangxianruangan granule (KXRG)-containing serum in inhibiting the differentiation of HOCs into HCCs via the Wnt-1/β-catenin signaling pathway. N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was applied to induce the transformation of the rat HOC cell line WB-F344 into HCCs. The overexpression plasmid, Wnt-1-up, was utilized to increase Wnt-1 expression. Subsequently, high, medium and low concentrations of KXRG were applied to MNNG-treated WB-F344 cells to assess the inhibitory effect of KXRG on cell differentiation. Flow cytometry was conducted to detect the cell cycle distribution, apoptotic rate and expression of cytokeratin-19 (CK-19) protein in cells. An immunofluorescence double staining protocol was used to detect the expression of Wnt-1 and β-catenin. ELISAs were performed to detect α fetoprotein in the cell supernatants.Reverse transcription-quantitative PCR and western blotting were conducted to detect the mRNA and protein expression levels of Wnt-1, β-catenin, Cyclin D1, C-myc, matrix metalloproteinase-7 (MMP-7), Axin2 and epithelial cell adhesion molecule (EpCAM) in cells. Compared with the normal group, the apoptotic rate, proportion of S phase cells, concentration of AFP in the cell supernatant, level of CK-19 protein, and mRNA and protein expression levels of Wnt-1, β-catenin, Cyclin D1, C-myc, MMP-7, Axin2 and EpCAM were all significantly increased in the model group. Addition of KXRG significantly reduced the aforementioned indicators compared with the model group. Moreover, Wnt-1 overexpression further increased the aforementioned indicators compared with the model group, whereas KXRG significantly inhibited these effects. The results indicated that KXRG inhibited the differentiation of HOCs into HCCs via the Wnt-1/β-catenin signaling pathway, which suggested the potential clinical application of KXRG for the prevention of hepatocellular carcinoma.

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Hepatocellular carcinoma stem cells origins and roles in hepatocarcinogenesis and disease progression

Cited by 27 publications

References 106 publications

Emerging Roles of C-Myc in Cancer Stem Cell-Related Signaling and Resistance to Cancer Chemotherapy: A Potential Therapeutic Target Against Colorectal Cancer

Emerging Roles of C-Myc in Cancer Stem Cell-Related Signaling and Resistance to Cancer Chemotherapy: A Potential Therapeutic Target Against Colorectal Cancer

The Role of KDM2B and EZH2 in Regulating the Stemness in Colorectal Cancer Through the PI3K/AKT Pathway

Kangxianruangan granule‑containing serum mediated inhibition of hepatic oval cell differentiation into hepatocellular carcinoma cells via the Wnt‑1/β‑catenin signaling pathway

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