Dishevelled 1-Regulated Superpotent Cancer Stem Cells Mediate Wnt Heterogeneity and Tumor Progression in Hepatocellular Carcinoma

Liao, Wen; Hsu, Chung Chi; Chan, Tze Sian; Yen, Chia Jui; Chen, Wei Yu; Pan, Hung Wei; Tsai, Kelvin K.

doi:10.1016/j.stemcr.2020.02.003

Cited by 23 publications

(32 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reilein et al found that the cell types of CSC-derivatives depend in part on the magnitude of spatially graded Wnt pathway activity. 53 The latest report 54 proves the remarkable heterogeneity in Wnt activity in HCC cells, among which Wnt-activity high ALDH1 + EpCAM + triple-positive cells are the most stem-like and highly tumorigenic cells in all CSC populations. This type of cells is called "superpotent CSCs" (spCSC).…”

Section: Wnt Signaling In Cancer Stemnessmentioning

confidence: 99%

<p>New Advances in Canonical Wnt/β-Catenin Signaling in Cancer</p>

Wen¹,

Wu²,

Awadasseid³

et al. 2020

CMAR

View full text Add to dashboard Cite

Wnt/β-catenin-mediated signaling is a key pathway regulating tissue growth and development, and tumorigenesis, and has received increasing attention in recent years. In addition to participating in healthy tissue and organ development, ectopic activation of the pathway can cause a variety of tumors and other pathologies. The pathway plays a critical role in many processes such as proliferation, differentiation, apoptosis, migration, invasion, epithelial–mesenchymal transition and cancer cell stemness. The importance of the Wnt signal is self-evident. This review describes the underlying mechanism of Wnt signaling pathway and highlights the latest findings on the relationship between Wnt signaling pathway and tumorigenesis. In addition, the potential relationship between miRNAs and Wnt signaling is presented. Furthermore, we discuss the intrinsic link between Wnt signaling and cancer cell stemness, which shed light on the malignant progression of tumor cells. Finally, cancer treatment strategies based on the canonical Wnt signaling pathway are summarized, hoping to help clinical development.

show abstract

Section: Wnt Signaling In Cancer Stemnessmentioning

confidence: 99%

<p>New Advances in Canonical Wnt/β-Catenin Signaling in Cancer</p>

Wen¹,

Wu²,

Awadasseid³

et al. 2020

CMAR

View full text Add to dashboard Cite

show abstract

“… 20 Of note, the expression of some CT proteins might be regulated posttranscriptionally; thus, the expression of CT gene mRNA may not guarantee protein expression, which therefore limits its generalization as candidate therapeutic targets. 9 Positive ASPM expression was detected in another HCC cohort, 58 and its prognostic value was also highlighted. The negative ASPM findings in our study might due to the heterogeneous expression pattern of CT genes, or the low sensitivity of the IHC antibody used.…”

Section: Discussionmentioning

confidence: 91%

Cancer-Testis Gene Expression in Hepatocellular Carcinoma: Identification of Prognostic Markers and Potential Targets for Immunotherapy

Zhang

Zhaorigetu

et al. 2020

Technol Cancer Res Treat

View full text Add to dashboard Cite

Background: Cancer-testis genes can serve as prognostic biomarkers and valuable targets for immunotherapy in multiple tumors because of their restricted expression in testis and cancer. However, their expression pattern in hepatocellular carcinoma is still not well understood. The purpose is to comprehensively characterize the cancer-testis gene expression in hepatocellular carcinoma as well as identify prognostic markers and potential targets for immunotherapy. Methods: Cancer-testis database and publicly available data sets reporting new cancer-testis genes were integrated, and then restricted them in a testis and hepatocellular carcinoma expression pattern. Pathway enrichment analysis and survival analysis were conducted to evaluate the biological function and prognostic effect of cancer-testis genes. Clustering analysis and coexpression analysis were performed to illustrate cancer-testis gene expression patterns in hepatocellular carcinoma. The association of gene expression of each cancer-testis gene to the corresponding methylation status was detected. Finally, we explored the associations between cancer-testis genes and CD8+ T-cell infiltration in hepatocellular carcinoma by TISIDB, and then validated it in an independent hepatocellular carcinoma cohort with 72 patients. Results: A total of 59 testis-specific genes were identified highly expressed in hepatocellular carcinoma. Pathway enrichment analysis revealed that cancer-testis genes in hepatocellular carcinoma significantly involves in the process of cell cycle regulation. Most of the cancer-testis genes were coexpressed, and cluster analysis suggested that cancer-testis gene expressed in hepatocellular carcinoma is independent of sex, hepatitis status, and histology type. We also found that demethylation might be a regulatory mechanism of cancer-testis gene expression in hepatocellular carcinoma. Survival analysis indicated that cancer-testis genes could predict the prognosis of patients with hepatocellular carcinoma. Furthermore, BUB1B was identified contributing to the resistance of CD8+ T-cell infiltration in hepatocellular carcinoma and was an independent prognostic factor both for overall survival and disease-free survival. Conclusions: Our analysis enables better understanding of cancer-testis genes in hepatocellular carcinoma and provides potential targets for hepatocellular carcinoma treatment. Experimental and clinical studies are needed for further validations.

show abstract

“…ASPM overexpression has been observed in various cancers ( Xu et al., 2019 , 2020 ; Zhou et al., 2020 ; Alsiary et al., 2014 ; Bruning-Richardson et al., 2011 ; Saleh et al., 2020 ; Xie et al., 2017 ; Tian and Wang, 2020 ; Timaner and Shaked, 2020 ; Hsu et al., 2019 ; Wang et al., 2013 ; Tang et al., 2019 ; Lin et al., 2008 ; Yuan et al., 2020 ; Wu et al., 2021 ) and thus might serve as a prognostic marker in various contexts. ASPM is a positive regulator of the canonical Wnt/β-catenin signaling ( Major et al., 2008 ; Hsu et al., 2019 ) and thus promotes cancer stemness and progression in prostate cancer ( Pai et al., 2019 ) and hepatocellular carcinoma ( Liao et al., 2020 ). Based on this information, and combined with our new data, we posit that ASPM could be a promising therapeutic target in cancers characterized by ASPM-overexpression.…”

Section: Discussionmentioning

confidence: 99%

ASPM promotes homologous recombination-mediated DNA repair by safeguarding BRCA1 stability

Wang

et al. 2021

iScience

View full text Add to dashboard Cite

Summary DNA double-strand break (DSB) repair by homologous recombination (HR) is essential for ensuring genome stability. Abnormal spindle-like microcephaly-associated ( ASPM ) gene encodes a spindle protein that is commonly implicated in primary microcephaly. We found that ASPM is recruited to sites of DNA damage in a PARP2-dependent manner. ASPM interacts with BRCA1 and its E3 ligase HERC2, preventing HERC2 from accessing to BRCA1 and ensuring BRCA1 stability. Inhibition of ASPM expression promotes HERC2-mediated BRCA1 degradation, compromises HR repair efficiency and chromosome stability, and sensitizes cancer cells to ionizing radiation. Moreover, we observed a synergistic effect between ASPM and PARP inhibition in killing cancer cells. This research has uncovered a novel function for ASPM in facilitating HR-mediated repair of DSBs by ensuring BRCA1 stability. ASPM might constitute a promising target for synthetic lethality-based cancer therapy.

show abstract

Dishevelled 1-Regulated Superpotent Cancer Stem Cells Mediate Wnt Heterogeneity and Tumor Progression in Hepatocellular Carcinoma

Cited by 23 publications

References 41 publications

<p>New Advances in Canonical Wnt/β-Catenin Signaling in Cancer</p>

<p>New Advances in Canonical Wnt/β-Catenin Signaling in Cancer</p>

Cancer-Testis Gene Expression in Hepatocellular Carcinoma: Identification of Prognostic Markers and Potential Targets for Immunotherapy

ASPM promotes homologous recombination-mediated DNA repair by safeguarding BRCA1 stability

Contact Info

Product

Resources

About