The Notch pathway promotes the cancer stem cell characteristics of CD90+ cells in hepatocellular carcinoma

Luo, Jing; Wang, Peng; Wang, Ronghua; Wang, Jinlin; Liu, Man; Xiong, Si; Li, Yawen; Cheng, Bin

doi:10.18632/oncotarget.6672

Cited by 64 publications

(56 citation statements)

References 33 publications

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“…Elevated expression of GDF15 was previously reported in serum and tumor samples of HCC patients [11]. To obtain further evidence that GDF15 expression is increased in HCC, we performed immunohistochemistry (IHC) on a human HCC tissue assay.…”

Section: Resultsmentioning

confidence: 99%

“…Most recently, the effect of CD90 + CSCs on enhanced cell motility of EpCAM + cancer stem cells was mediated, at least in part, via activation of TGF-β signaling by CD90 + CSCs [10]. Similar evidence demonstrated that liver-specific Notch signaling activation was associated with tumorigenesis and metastasis of LCSCs [11]. All these studies demonstrate that LCSCs are a pivotal therapeutic target in the eradication of HCC.…”

Section: Introductionmentioning

confidence: 88%

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Growth differentiation factor 15 induces growth and metastasis of human liver cancer stem-like cells via AKT/GSK-3β/β-catenin signaling

et al. 2017

Oncotarget

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Cancer stem cells in liver cancer are thought to be responsible for tumor recurrence and metastasis. However, the factors that mediate this mechanism have yet to be completely elucidated. In this study, we isolated CD13+CD44+ sphere cells (SCs) derived from liver cancer tissues and SK-Hep-1 cells, which possessed cancer stem cell-like properties. Through cytokine array analysis, growth differentiation factor 15 (GDF15) was significantly increased in SCs. Clinical data showed GDF15 was overexpressed in liver cancer tissues and was positively related to pathological grading. GDF15 knockdown significantly inhibited the growth and metastasis of SCs through AKT/GSK-3β/β-catenin pathway suppression. Moreover, a PI3K inhibitor LY294002 inhibited AKT/GSK-3β/β-catenin pathway activated by GDF15 and attenuated GDF15-induced proliferation, colony formation and invasion of SCs. Conclusion: Our studies suggest that CD13+CD44+ SCs may represent a subset of LCSCs. GDF15 promotes the growth and metastasis of SCs by activating AKT/GSK-3β/β-catenin signaling pathway. Promisingly, GDF15 could be considered as a potential therapeutic target in liver cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 88%

Growth differentiation factor 15 induces growth and metastasis of human liver cancer stem-like cells via AKT/GSK-3β/β-catenin signaling

et al. 2017

Oncotarget

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“…It was recently shown that increases in colony-forming capacity, invasiveness, and migratory ability were associated with other CSC characteristics, such as selfrenewal, in hepatocellular carcinoma and promoted tumor initiation and growth, leading to metastasis. 41 In addition, it was reported that suppression of FBXW7 increased the expression of OCT4 and NANOG in CC cells and that the cells formed tumor spheres, which indicated promotion of the CSC-like capability of CC cells. 16 The increased self-renewal capacity observed in our study could be due to NOTCH1 accumulation resulting from FBXW7 suppression in CC.…”

Section: Discussionmentioning

confidence: 97%

FBXW7 modulates malignant potential and cisplatin‐induced apoptosis in cholangiocarcinoma through NOTCH1 and MCL1

et al. 2018

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The ubiquitin ligase F‐box and WD repeat domain‐containing 7 (FBXW7) is responsible for degrading diverse oncoproteins and is considered a tumor suppressor in many human cancers. Inhibiting FBXW7 enhances the malignant potential of several cancers. In this study, we aimed to investigate the role of FBXW7 in cholangiocarcinoma. We found that FBXW7 expression was associated with clinicopathological outcomes in cholangiocarcinoma patients. Both disease‐free and overall survival were significantly worse in the low‐FBXW7 group than in the high‐FBXW7 group (P = .001 and P < .001, respectively). Multivariate analysis with the Cox proportional hazards model indicated that FBXW7 was the most important independent prognostic factor for disease‐free (P = .006) and overall (P = .0004) survival. We also showed that the two FBXW7 substrates, NOTCH1 and myeloid cell leukemia sequence 1 (MCL1), regulate cholangiocarcinoma progression. Depletion of FBXW7 resulted in NOTCH1 accumulation and increased cholangiocarcinoma cell migration and self‐renewal. Interestingly, when cells were stimulated with cis‐diamminedichloridoplatinum(II) (cisplatin), FBXW7 suppression induced MCL1 upregulation, which reduced the sensitivity of cholangiocarcinoma cells to apoptosis, indicating that FBXW7‐mediated ubiquitylation is context‐dependent. These results indicate that FBXW7 modulates the malignant potential of cholangiocarcinoma through independent regulation of NOTCH1 and MCL1.

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“…Obviously, the high expression of Thy-1, its localization in lipid rafts, and high carbohydrate content allow its interaction with different receptors, which results in the control of their activity. By acting in cis or trans, Thy-1 is able to interfere with several signaling pathways, including Smad, wingless-type mouse mammary tumor virus integration site (Wnt), Src, notch, and peroxisome proliferator-activated receptor g (Pparg) (22,26,27,(29)(30)(31)(32)(33)(34).…”

Section: Structure Of Thy-1 and Signaling Cascadesmentioning

confidence: 99%

Thy‐1: more than a marker for mesenchymal stromal cells

Saalbach

Anderegg

2019

FASEB j.

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Balanced differentiation of mesenchymal stromal cells (MSCs) into osteoblasts and adipocytes is essential for healthy bone and fat homeostasis. A disturbed balance of MSC differentiation results in bone loss and increased adipogenesis as observed in several human conditions, such as osteoporosis, obesity, and aging. This reflects the importance of MSC fate decision. Therefore, it is important to identify factors that regulate the balance between osteogenic and adipogenic differentiation of MSCs so as to identify new targets to improve bone formation in osteoporosis and control adipose tissue development. There is accumulating evidence that thymus cell antigen 1 (Thy‐1), also known as CD90, expressed on MSCs, plays a critical role in the fate decision of MSCs. Recently, Thy‐1 has been shown to promote osteogenic differentiation of MSCs and thus bone formation while inhibiting adipogenic differentiation and restricting adipose tissue accumulation. The clinical importance of these findings was validated by the detection of reduced serum soluble Thy‐1 in patients with disturbed bone remodeling. In this review, we aim to summarize data on the impact of Thy‐1 on the control of MSC differentiation and its consequences for bone and fat formation.—Saalbach, A., Anderegg, U. Thy‐1: more than a marker for mesenchymal stromal cells. FASEB J. 33, 6689–6696 (2019). http://www.fasebj.org

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The Notch pathway promotes the cancer stem cell characteristics of CD90+ cells in hepatocellular carcinoma

Cited by 64 publications

References 33 publications

Growth differentiation factor 15 induces growth and metastasis of human liver cancer stem-like cells via AKT/GSK-3β/β-catenin signaling

Growth differentiation factor 15 induces growth and metastasis of human liver cancer stem-like cells via AKT/GSK-3β/β-catenin signaling

FBXW7 modulates malignant potential and cisplatin‐induced apoptosis in cholangiocarcinoma through NOTCH1 and MCL1

Thy‐1: more than a marker for mesenchymal stromal cells

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