β-Catenin signaling in hepatocellular carcinoma

Xu, Cenke; Xu, Zhenhe; Zhang, Yi; Evert, Matthias; Calvisi, Diego F.; Chen, Xin

doi:10.1172/jci154515

Cited by 143 publications

(92 citation statements)

References 153 publications

(151 reference statements)

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“…Accumulation of cytoplasmic β‐catenin and subsequent translocation to the nucleus are the typical markers for the Wnt/β‐catenin pathway activation. 34 WB and IF assays consistently verified the decreased cytoplasmic/nuclear β‐catenin in Huh7‐shDDX55 cells and the upregulated cytoplasmic/nuclear β‐catenin in SNU387‐oeDDX55 cells compared to the corresponding controls (Figure 4B ‐C).…”

Section: Resultsmentioning

confidence: 53%

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DDX55 promotes hepatocellular carcinoma progression by interacting with BRD4 and participating in exosome‐mediated cell‐cell communication

Zhou

Long

et al. 2022

Cancer Science

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The involvement of DEAD‐box helicase 55 (DDX55) in oncogenesis has been suggested, but its biological role in hepatocellular carcinoma (HCC) remains unknown. The present study verified the upregulation of DDX55 in HCC tissues compared with non‐tumor controls. DDX55 displayed the highest prognostic values among the DEAD‐box protein family for recurrence‐free survival and overall survival of HCC patients. In addition, the effects of DDX55 in the promotion of HCC cell proliferation, migration, and invasion were determined ex vivo and in vivo. Mechanistically, we revealed that DDX55 could interact with BRD4 to form a transcriptional regulatory complex that positively regulated PIK3CA transcription. Following that, β‐catenin signaling was activated in a PI3K/Akt/GSK‐3β dependent manner, thus inducing cell cycle progression and epithelial–mesenchymal transition. Intriguingly, both DDX55 mRNA and protein were identified in the exosomes derived from HCC cells. Exosomal DDX55 was implicated in intercellular communication between HCC cells with high or low DDX55 levels and between HCC cells and endothelial cells, thereby promoting the malignant phenotype of HCC cells and angiogenesis. In conclusion, DDX55 may be a valuable prognostic biomarker and therapeutic target in HCC.

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Section: Resultsmentioning

confidence: 53%

“… 46 , 52 , 53 , 54 A high percentage of aberrant activation of the Wnt/β‐catenin signaling (30%–40%) and the PI3K/Akt signaling (nearly 50%) have been reported in human HCC samples, which highlights the potential of DDX55 as a valuable therapeutic target in those HCC. 34 , 55 …”

Section: Discussionmentioning

confidence: 99%

DDX55 promotes hepatocellular carcinoma progression by interacting with BRD4 and participating in exosome‐mediated cell‐cell communication

Zhou

Long

et al. 2022

Cancer Science

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“…In the GO term-based enrichment analysis ( Figure S4A , Table S3 ), we found that upregulation of the Rho pathway changed the cell morphology under hypoxia, thereby promoting the expansion and metastasis of HCC ( 42 ). Hypoxia promoted HCC metastasis through the WNT signaling pathway ( 43 ). Hypoxia also inhibited the differentiation of immature B cells, while also downregulating complement activation and apoptotic signaling.…”

Section: Resultsmentioning

confidence: 99%

A Novel hepatocellular carcinoma specific hypoxic related signature for predicting prognosis and therapeutic responses

et al. 2022

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Hypoxia is an important feature of the tumor microenvironment(TME) and is closely associated with cancer metastasis, immune evasion, and drug resistance. However, the precise role of hypoxia in hepatocellular carcinoma(HCC), as well as its influence on the TME, and drug sensitivity remains unclear. We found the excellent survival prediction value of Hypoxia_DEGs_Score model. In hypoxic HCC, somatic mutation, copy number variation, and DNA methylation were closely related to hypoxic changes and affected tumorigenesis, progression, metastasis, and drug resistance. In HCC, aggravated hypoxic stress was found to be accompanied by an immune exclusion phenotype and increased infiltration of immunosuppressive cells. In the validation cohort, patients with high Hypoxia_DEGs_Score were found to have worse immunotherapeutic outcomes and prognoses, and may benefit from drugs against cell cycle signaling pathways rather than those inhibiting the PI3K/mTOR pathway. Hypoxia_DEGs_Score has an excellent predictive capability of changes in the TME, the efficacy of immunotherapy, and the response of drugs. Therefore, Hypoxia_DEGs_Score can help develop personalized immunotherapy regimens and improve the prognosis of HCC patients.

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“…In early HCC, surgical procedures, including resection and liver transplantation, remain the only therapeutic choices, whereas late-stage HCC is essentially untreatable. To develop the diagnosis and treatment of HCC, new biomarkers and targeted therapies are critically required [ 305 ]. Metastasis seems to be a significant factor affecting long-term survival in patients with severe HCC [ 306 ].…”

Section: Lncrnas As Diagnostic and Therapeutic Markers In Hccmentioning

confidence: 99%

Function of the Long Noncoding RNAs in Hepatocellular Carcinoma: Classification, Molecular Mechanisms, and Significant Therapeutic Potentials

Khan

Zhang

2022

Bioengineering

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Hepatocellular carcinoma (HCC) is the most common and serious type of primary liver cancer. HCC patients have a high death rate and poor prognosis due to the lack of clear signs and inadequate treatment interventions. However, the molecular pathways that underpin HCC pathogenesis remain unclear. Long non-coding RNAs (lncRNAs), a new type of RNAs, have been found to play important roles in HCC. LncRNAs have the ability to influence gene expression and protein activity. Dysregulation of lncRNAs has been linked to a growing number of liver disorders, including HCC. As a result, improved understanding of lncRNAs could lead to new insights into HCC etiology, as well as new approaches for the early detection and treatment of HCC. The latest results with respect to the role of lncRNAs in controlling multiple pathways of HCC were summarized in this study. The processes by which lncRNAs influence HCC advancement by interacting with chromatin, RNAs, and proteins at the epigenetic, transcriptional, and post-transcriptional levels were examined. This critical review also highlights recent breakthroughs in lncRNA signaling pathways in HCC progression, shedding light on the potential applications of lncRNAs for HCC diagnosis and therapy.

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β-Catenin signaling in hepatocellular carcinoma

Cited by 143 publications

References 153 publications

DDX55 promotes hepatocellular carcinoma progression by interacting with BRD4 and participating in exosome‐mediated cell‐cell communication

DDX55 promotes hepatocellular carcinoma progression by interacting with BRD4 and participating in exosome‐mediated cell‐cell communication

A Novel hepatocellular carcinoma specific hypoxic related signature for predicting prognosis and therapeutic responses

Function of the Long Noncoding RNAs in Hepatocellular Carcinoma: Classification, Molecular Mechanisms, and Significant Therapeutic Potentials

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