LEF1 Enhances the Progression of Colonic Adenocarcinoma via Remodeling the Cell Motility Associated Structures

Li, Xiao; Zhang, Caixia; Li, Xinyao; Jia, Chenshuang; Chen, Lirong; Yue, Yuan; Gao, Qian; Feng, Yali; Zhao, Ruixia; Zhao, Xuewei; Cheng, Sinan; Shu, Zhan; Xu, Jie; Duan, Wei; Nie, Guochao; Hou, Yingchun

doi:10.3390/ijms221910870

Cited by 17 publications

(13 citation statements)

References 39 publications

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“…The various anticancer effects of juglone indicate it has the potential to become an anticancer drug. However, due to the biological toxicity of juglone, it is necessary to modify its chemical structure to improve bioavailability and reduce its toxicity [28]. In addition, novel drug delivery systems, such as liposome encapsulation, may be an appropriate method to improve juglone pharmacokinetic properties [29].…”

Section: Discussionmentioning

confidence: 99%

Juglone Inhibits Tumor Metastasis by Regulating Stemness Characteristics and the Epithelial-to-Mesenchymal Transition in Cancer Cells both in Vitro and in Vivo

Zou¹,

Yu²,

Wang³

et al. 2023

Front. Biosci. (Landmark Ed)

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Background:The stemness characteristics of cancer cells, such as self-renewal and tumorigenicity, are considered to be responsible, in part, for tumor metastasis. Epithelial-to-mesenchymal transition (EMT) plays an important role in promoting both stemness and tumor metastasis. Although the traditional medicine juglone is thought to play an anticancer role by affecting cell cycle arrest, induction of apoptosis, and immune regulation, a potential function of juglone in regulating cancer cell stemness characteristics remains unknown. Methods: In the present study, tumor sphere formation assay and limiting dilution cell transplantation assays were performed to assess the function of juglone in regulating maintenance of cancer cell stemness characteristics. EMT of cancer cells was assessed by western blot and transwell assay in vitro, and a liver metastasis model was also performed to demonstrate the effect of juglone on colorectal cancer cells in vivo. Results: Data gathered indicates juglone inhibits stemness characteristics and EMT in cancer cells. Furthermore, we verified that metastasis was suppressed by juglone treatment. We also observed that these effects were, in part, achieved by inhibiting Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1). Conclusions: These results indicate that juglone inhibits maintenance of stemness characteristics and metastasis in cancer cells.

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Section: Discussionmentioning

confidence: 99%

Juglone Inhibits Tumor Metastasis by Regulating Stemness Characteristics and the Epithelial-to-Mesenchymal Transition in Cancer Cells both in Vitro and in Vivo

Zou¹,

Yu²,

Wang³

et al. 2023

Front. Biosci. (Landmark Ed)

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“…LEF1 contains a β-catenin-binding domain, a context-dependent regulatory domain, a high-mobility group DNA-binding domain (HMG), and a nuclear localization sequence 38. There is evidence that LEF1 can induce epithelial-mesenchymal transition (EMT) in the absence of β-catenin, potentially via its HMG domain 39,40. LEF1 also responds to Notch, and the effects do not appear to depend on Wnt signaling components 41.…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of LEF1 and β-Catenin in Invasive Micropapillary Carcinoma of the Breast is Associated With Lymphovascular Invasion and Lymph Node Metastasis

Dolezal

Zhang

Harigopal

2022

Applied Immunohistochemistry &Amp; Molecular Morphology

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Invasive micropapillary breast carcinoma (IMPC) is a rare breast cancer subtype characterized by small tumor cell clusters with loss of stromal attachment, an inside-out growth appearance, and lymphotropism. IMPC is associated with high incidence of lymphovascular invasion (LVI) and lymph node metastasis. Activated Wnt signaling has been implicated in the metastasis of other aggressive breast tumors, including triple-negative and basal-like carcinomas. In this study, we tested whether activated Wnt signaling could be detected in IMPC. Upon ligand binding, the central mediator of the Wnt pathway, β-catenin, accumulates in the cytosol and translocates to the nucleus where it forms a complex with lymphoid enhancer-binding factor 1 (LEF1) to regulate transcription. We performed immunostaining for β-catenin and LEF1 on a well-annotated cohort of 40 breast tumors and nodal metastases displaying micropapillary histopathology. Strong nuclear accumulation of β-catenin was not observed, however a dim cytosolic and/or nuclear accumulation of β-catenin was sometimes seen in IMPC and this expression pattern was significantly associated with nodal metastasis. β-catenin expression correlated with the upregulation of LEF1 in IMPC. LEF1 expression was detected in 26 of 40 (65%) cases and was specifically enriched at the invasive front of the tumor and in tumor clusters undergoing LVI. Detection of LEF1 expression in the primary tumor was associated with an increased rate of LVI, lymph node metastasis, and disease relapse. LEF1 and β-catenin expression levels were significantly higher in metastases compared with primary tumors. In summary, this study demonstrates an association between the upregulation of β-catenin/LEF1 and the metastasis of IMPC.

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“…STRING analysis also revealed the complex interaction of CTNNB1, Sox 17, 30, LEF1, and TCF7L1 in beta-catenin binding. LEF1 (lymphoid enhancer-binding factor 1) shares significant homology with HMG protein and are involved in Wnt canonical pathway, cell differentiation, and follicle morphogenesis (Xiao et al, 2021). Pax3, Sox10, and c-Ret are components of a neural crest development pathway, and interruption of this pathway at various stages results in neural crest–related human genetic syndromes (Lang et al, 2000)…”

Section: Discussionmentioning

confidence: 99%

Molecular evolution and inheritance pattern of Sox gene family among Bovidae

Akinyemi

Adegbaju

Grytsay

et al. 2022

Preprint

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Sox gene is an evolutionarily conserved family of transcription factors that play important roles in cellular differentiation and numerous complex developmental processes. In vertebrates, Sox proteins are required for cell fate decision, morphogenesis, and control self-renewal in embryonic and adult stem cells. Sox gene family has been well studied in multiple species including humans but scanty or no study in Bovidae. In this study, we conducted a detailed evolutionary analysis of this gene family in Bovidae, including their physicochemical properties, biological functions, and patterns of inheritance. We performed a genome-wide cataloguing to explore the Sox gene family using multiple bioinformatics tools. Our analysis revealed conserved motifs that are crucial to the ability of Sox genes to interact with the regulatory regions of target genes and orchestrate multiple developmental and physiological processes. Importantly, we report a unique motif being EFDQYL/ELDQYL found in SoxE and SoxF groups. Further analysis revealed that this motif sequence accounts for the binding and transactivation potential of Sox proteins. Protein-protein interaction showed significant interaction among Sox genes and related genes implicated in embryonic development and the regulation of cell differentiation. We conclude that Sox gene family uniquely evolved among Bovidae with a few exhibiting important motifs that drives several developmental and physiological processes.

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LEF1 Enhances the Progression of Colonic Adenocarcinoma via Remodeling the Cell Motility Associated Structures

Cited by 17 publications

References 39 publications

Juglone Inhibits Tumor Metastasis by Regulating Stemness Characteristics and the Epithelial-to-Mesenchymal Transition in Cancer Cells both in Vitro and in Vivo

Juglone Inhibits Tumor Metastasis by Regulating Stemness Characteristics and the Epithelial-to-Mesenchymal Transition in Cancer Cells both in Vitro and in Vivo

Increased Expression of LEF1 and β-Catenin in Invasive Micropapillary Carcinoma of the Breast is Associated With Lymphovascular Invasion and Lymph Node Metastasis

Molecular evolution and inheritance pattern of Sox gene family among Bovidae

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