ALDH1A1 maintains the cancer stem-like cells properties of esophageal squamous cell carcinoma by activating the AKT signal pathway and interacting with β-catenin

Wang, Wei; He, Songbing; Zhang, Renya; Peng, Jie; Guo, Daolu; Zhang, Jinguo; Xiang, Bo; Li, Lei

doi:10.1016/j.biopha.2020.109940

Cited by 31 publications

(30 citation statements)

References 31 publications

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“…in the CD133 + cell group were identified under the light microscope, most of them were polynuclear cells in NPC cells [25]. In our study, CD133 + cells contained more large and small cells than CD133cells, the large cells are PGCCs and the small cells maybe the daughter cells of PGCCs, and medium size cells are non tumor-stem cells.…”

Section: Discussionmentioning

confidence: 47%

“…Immunofluorescence and confocal microscopy were performed as our previously reported [24,25] . Images were captured by using a Zeiss confocal microscope.…”

Section: Immunohistochemistry (Ihc) and Immunofluorescence (If)mentioning

confidence: 99%

“…Sphere formation assay was performed as our previously reported [25,26] . The KYSE-150 and TE-1 cells were seeded in low-attachment six-well culture plates (Corning, NY, USA) at a density of 1 × 10 4 cells per well under serum-free conditions consisting of DMEM/F-12 (Life Technologies), 20 ng/mL epidermal growth factor (Invitrogen), 20 ng/mL basic fibroblast growth factor (Invitrogen), and 20 μL/mL B27 (Life Technologies).…”

Section: Sphere-formation Assaymentioning

confidence: 99%

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miR-378d Regulates Polyploidization and Malignant Phenotype of Tumor Cells Through AKT and RhoA

W¹,

Peng²,

Shu³

et al. 2021

Preprint

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Studies have shown that stress such as hypoxia, chemotherapy, radiotherapy can lead to polyploidization of tumor cells, which play an important role in tumor heterogeneity and malignant phenotype. Paclitaxel (PTX) treatment promoted polyploid cancer cells (PCCs) formation, and miR-378d is sharply reduced in PCCs of esophageal squamous cell carcinomas (ESCC) cells, but miR-378d participation PCCs formation and the impact on the biological behavior of ESCC remains unclear. We analyzed the PCCs formation and biological behavior of ESCC cells in vivo and in vitro, and the related proteins regulated by miR-378d. Results showed that miR-378d expression was associated with good prognosis in ESCC patients. miR-378d inhibition promoted PCCs formation, heterogenicity, chemo-resistance, monoclonal formation, EMT, migration, invasion, stemness and metastasis of ESCC cells. miR-378d can target downregulated AKT1, and inactivating the AKT-β-catenin signaling pathway, miR-378d and AKT can also regulated RhoA expression. AKT and RhoA regulated polyploidization and depolyploidization. Therefore, miR-378d expression is a good prognostic factor of ESCC patients and regulates polyploidization and malignant phenotype of tumor cells through AKT and RhoA.

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Section: Discussionmentioning

confidence: 47%

“…Immunofluorescence and confocal microscopy were performed as our previously reported [24,25] . Images were captured by using a Zeiss confocal microscope.…”

Section: Immunohistochemistry (Ihc) and Immunofluorescence (If)mentioning

confidence: 99%

Section: Sphere-formation Assaymentioning

confidence: 99%

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miR-378d Regulates Polyploidization and Malignant Phenotype of Tumor Cells Through AKT and RhoA

W¹,

Peng²,

Shu³

et al. 2021

Preprint

Self Cite

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“…β-catenin, a core member of the canonical Wnt signaling pathway, was strongly linked to EC progression, metastasis, and invasion [40][41][42][43]. In off state of canonical Wnt signaling pathways, β-catenin is mainly expressed at the cytoplasm, and Gsk-3β inhibits tumor growth by degrading β-catenin.…”

Section: Discussionmentioning

confidence: 99%

NRAGE, a potential biomarker, induces radioresistance in two- and three-dimensional culture and confers poor prognosis in esophageal squamous cell carcinoma

Hong-bin¹,

Wang²,

Xiao³

et al. 2020

Preprint

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Background To explore the mechanism of NRAGE enhancing radioresistance of ESCC in 2D and 3D levels. Methods Stably NRAGE-overexpressed ESCC cells and 3D-printing models for ESCC cells were established. Then, cellular malignancy indexes, such as cell morphology, proliferation, radioresistance, motility, apoptosis, cell cycle, and proteins of the Wnt/β-catenin pathway, were compared between radioresistant and its parental cells in 2D and 3D levels. Additionally, 44 paraffin ESCC specimens with radical radiotherapy were selected to examine NRAGE and β-catenin protein expression and analyze the clinical correlation. Results Experiments in 2D culture showed that Eca109/NRAGE cells’ morphology was more irregular, elongated spindle-shaped and disappeared polarity. It obtained faster growth ability, stronger resistance to irradiation, enhanced motility, reduced apoptosis ratio and cell cycle rearrangement. Moreover, Western blot results showed β-catenin, p-Gsk-3β and CyclinD1 expressions were induced, while p-β-catenin and Gsk-3β expressions decreased in Eca109/NRAGE cells. Experiments in the 3D-printing model showed Eca109/NRAGE cell-laden 3D scaffolds had the advantage on growth and spheroiding according to the brigbtfield observation, scanning electron microscopy and Ki-67 IHC staining, and higher expression at the β-catenin protein. Clinical analysis showed that NRAGE expression was higher in tumor tissues than in control tissues of ESCC patients from the Public DataBase. Compared with radiotherapy effective group, both NRAGE total and nuclear and β-catenin nuclear expressions were significantly upregulated from ESCC specimens in invalid group. Further analysis showed a positive and linear correlation between NRAGE nuclear and β-catenin nuclear expressions. Additionally, results from univariate and multivariate analyses revealed NRAGE nuclear expression could serve as a risk factor for ESCC patients receiving radical radiotherapy. Conclusion ESCC cells with NRAGE nuclear accumulation demonstrated greater radioresistance, which may be related to the activation of the Wnt/β-catenin signaling pathway. It indicated that NRAGE nuclear expression was a potential biomarker for monitoring radiotherapeutic response.

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“…. We have previously reported that AKT-β-catenin-ALDH1A1 can form a positive feedback regulatory loop to promote the characteristics of cancer stem cells (CSCs) [38,39]. .…”

Section: Discussionmentioning

confidence: 99%

Absence of miR-378d Promoted The Malignant Phenotype of ESCC Through The AKT-β-Catenin and Hippo-p53 Signaling Pathway

Peng

Liu

et al. 2020

Preprint

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Background: Chemoresistance is an important cause of malignant progression of esophageal squamous cell carcinomas (ESCCs). miR-378d is sharply reduced in paclitaxel (PTX)-resistance esophageal cancer cells by gene-expression profile analysis (RNA-Seq), but the mechanism of miR-378d-mediated tumor progression is unclear. Patients and methods: Herein, we detected miR-378d expression in 596 ESCC patients by in situ hybridization. Results showed that low miR-378d expression was associated with poor prognosis of ESCC patients, and that miR-378d absence enhanced carcinogenesis by promoting chemoresistance, colony formation, EMT, invasion, and metastasis. Results: Furthermore, miR-378d can target downregulated AKT1 expression by binding to the AKT1 mRNA 3′UTR, inactivating the AKT-β-catenin signaling pathway, and reducing the epithelial–mesenchymal transition marker Vimentin and the cancer stem cell marker ALDH1A1. miR-378d silencing in ESCC cells also promoted polyploidy formation in vitro and in vivo, and miR-378d inhibition suppressed the Hippo-p53 signaling pathway. Consequnetly, YAP and TAZ protein accumulated in nuclei and p53 expression decreased, which may promote the formation of ploidy tumor cells. Conclusions: Therefore, low miR-378d expression is a poor prognostic factor of ESCC patients and promotes polyploidy and cancer progression by activating AKT-β-catenin and suppressing the Hippo-p53 signaling pathway.

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ALDH1A1 maintains the cancer stem-like cells properties of esophageal squamous cell carcinoma by activating the AKT signal pathway and interacting with β-catenin

Cited by 31 publications

References 31 publications

miR-378d Regulates Polyploidization and Malignant Phenotype of Tumor Cells Through AKT and RhoA

miR-378d Regulates Polyploidization and Malignant Phenotype of Tumor Cells Through AKT and RhoA

NRAGE, a potential biomarker, induces radioresistance in two- and three-dimensional culture and confers poor prognosis in esophageal squamous cell carcinoma

Absence of miR-378d Promoted The Malignant Phenotype of ESCC Through The AKT-β-Catenin and Hippo-p53 Signaling Pathway

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