PAX3 Promotes Cell Migration and CXCR4 Gene Expression in Neural Crest Cells

Xu, Man; Li, Yongle; Du, Jinfeng; Lin, Hengrong; Cao, Sixian; Mao, Zuming; Wu, Ronghua; Liu, Yan; Yin, Qiyou

doi:10.1007/s12031-017-0995-9

Cited by 9 publications

(6 citation statements)

References 21 publications

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“…We retrieved 475 targets of Pax3 expressed in the SC NC dataset, among a total of 657 targets found in the whole embryo (Table S6). Known targets such as cxcr4 and prtg were validated ( 46, 48 ). Among the 475 targets, 80 were also predicted by GRN-Boost2 modelling including psmd4, psen2, sp7, notch1, hnf1b.…”

Section: Resultsmentioning

confidence: 99%

“…We verified direct Pax3-binding targets in vivo using ChIPseq on mid-neurula stage embryos (Figure 4B) and identified 657 potential targets in the whole embryo, of which 475 were expressed in the SC NC dataset (Supplementary file 1 -Table S6), including known direct targets, e.g. cxcr4 and prtg (Plouhinec et al, 2014;Xu et al, 2018).…”

Section: Defining the Diversity Of Premigratory Neural Crest Statesmentioning

confidence: 95%

“…Known targets such as cxcr4 and prtg were validated (46,48). Among the 475 targets, 80 were also predicted by GRN-Boost2 modelling including psmd4, psen2, sp7, notch1, hnf1b.…”

Section: Large Scale Experimental Validation Of Grnboost2 Model Predi...mentioning

confidence: 99%

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From neural border to migratory stage: A comprehensive single cell roadmap of the timing and regulatory logic driving cranial and vagal neural crest emergence

Kotov

Alkobtawi

Seal

et al. 2022

Preprint

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Neural crest cells exemplify cellular diversification from a multipotent progenitor population. However, the full sequence of molecular choices orchestrating the emergence of neural crest heterogeneity from the embryonic ectoderm remains elusive. Gene-regulatory-networks (GRN) govern early development and cell specification towards definitive neural crest. Here, we combine ultra-dense single cell transcriptomes with machine-learning and large-scale experimental validation to provide a comprehensive GRN underlying neural crest fate diversification from induction to early migration stages. During gastrulation, a transient neural border zone state precedes choice between neural crest and placodes following a "dual convergence model". Transcription factor connectome and bifurcation analyses demonstrate the early emergence of neural crest fates at neural plate stage, alongside an unbiased multipotent lineage persisting until after epithelial-mesenchymal transition. We decipher the circuits driving cranial and vagal neural crest formation and provide a broadly applicable strategy for investigating SC transcriptomes in vertebrate GRNs in development, evolution and disease.

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Section: Resultsmentioning

confidence: 99%

Section: Defining the Diversity Of Premigratory Neural Crest Statesmentioning

confidence: 95%

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From neural border to migratory stage: A comprehensive single cell roadmap of the timing and regulatory logic driving cranial and vagal neural crest emergence

Kotov

Alkobtawi

Seal

et al. 2022

Preprint

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“…Increasing evidence indicated that the decreased cell migration property may be related to the downregulation of CXCR4 [ 26 – 28 ]. In addition, Xu et al [ 29 ] reported that PAX3 may facilitate the migration of neural crest cells by increasing the CXCR4 expression. To the best of our knowledge, there have been few studies on the effect of ginsenoside Rb1 on the SDF-1/CXCR4 axis.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rb1 Modulates the Migration of Bone-Derived Mesenchymal Stem Cells through the SDF-1/CXCR4 Axis and PI3K/Akt Pathway

Liu

et al. 2022

Disease Markers

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Background and Objectives. Bone mesenchymal stem cells (BMSCs) play a vital role in skin wound healing and skin regeneration through proliferation, migration, and paracrine interactions. A previous study indicated that ginsenoside Rb1 acted as a vital antidotal component which antagonized the oxidative stem cell. However, the effect and mechanism of ginsenoside Rb1-mediated BMSC migration remained unknown. Methods. Wound-healing assay and Transwell assay were utilized to evaluate the effect of ginsenoside Rb1 on the migration of BMSCs. RT-PCR and Western blotting were performed to evaluate the expression of stromal-derived factor 1 (SDF-1), C-X-C chemokine receptor type 4 (CXCR4), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (PKB; AKT). Results. Ginsenoside Rb1 significantly enhanced the migration of BMSCs through the activation of SDF-1, CXCR4, p-PI3K/PI3K, and p-Akt/Akt relative expression. Furthermore, this stimulus was blocked by the pretreatment with AMD3100 and LY294002. Conclusions. Ginsenoside Rb1 facilitated the migration of BMSCs through the activation of the SDF-1/CXCR4 axis and PI3K/Akt pathway.

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“…The CXCR4 chemokine receptor and its ligand CXCL12 (SDF-1) are one of the beststudied chemokine systems in tumor biology. In gliomas, the CXCL12/CXCR4 axis regulates multiple mechanisms that sustain tumor proliferation, migration and angiogenesis [17][18][19]. CXCL12 is the only known chemokine that binds CXCR4.…”

Section: Introductionmentioning

confidence: 99%

Cancer stem-like cells of nasopharyngeal carcinoma express CXCR4 and display highly invasive activity

Zhu

Liu

et al. 2022

Preprint

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Background: Nasopharyngeal carcinoma (NPC) patients with distant metastasis have a poor response to conventional first-line chemoradiotherapy and a poor prognosis. Growing evidence suggests that a subpopulation of cancer stem cells (CSCs) with certain markers is essential for cancer metastasis. However, the unique subset of CSCs that drives NPC metastasis is still unclear. Methods: Immunohistochemistry was used to analyze the expression characteristics, distribution and relationship of CXCR4 with clinical parameters in nasopharyngeal carcinoma. The expression characteristics of CD133 and CXCR4 in nasopharyngeal carcinoma tumorspheres were analyzed by flow cytometry. Through a magnetic activated cell sorting system, CXCR4-positive and CXCR4-negative tumorsphere cells were obtained, and then, the differences in invasion (in vitro and in vivo), metastatic tumor formation, stemness and EMT characteristics of the two cell types were compared. SDF-1 and its inhibitor were used to explore the roles of stromal-cell derived factor-1 (SDF-1) in the metastatic process. Results: In 71 cases of human nasopharyngeal carcinoma, CXCR4 expression was correlated with T stage and N stage. The CXCR4-positive rate of the tumor cells in the T3-4 group was higher than that in the T1-2 group (60.6% vs 28.9%, P =0.009), and that in the N2-3 group was higher than that in the N0-1 group (76.5% vs 13.5%, P=0.000). The CXCR4 expression level was higher in cells with high metastasis or low differentiation. The culture of tumor spheres enriched CD133-positive and CXCR4-positive cells, and most CD133-positive cells also expressed CXCR4 in NPC. The secondary tumorsphere-forming rate of the CXCR4-positive tumorsphere cells was higher than that of the CXCR4-negative tumorsphere cells, and most of the CXCR4-positive tumorsphere cells had a spindle morphology. The CXCR4-positive tumorsphere cells had stronger migration and invasion ability in vitro and metastatic tumor formation ability in mice, which depends on the SDF-1/CXCR4 axis, than the CXCR4-negative tumorsphere cells.Compared with those of the CXCR4-negative tumorsphere cells, the mRNA expression levels of Oct4, Nanog, Sox2, Snail, Twist, Vimentin and N-cadherin in the CXCR4-positive tumor tumorsphere cells were increased, while E-cadherin decreased, and the protein expression levels of Vimentin and N-cadherin increased, while that of E-cadherin decreased. Conclusion: Therefore, CXCR4 may be a marker of nasopharyngeal metastatic tumor stem cells, and CXCR4 may be involved in tumor stem cell migration and invasion by regulating the EMT process. These results suggest that targeting the SDF1/CXCR4 axis may interfere with nasopharyngeal carcinoma tumor stem cell migration and invasion and provide new treatment strategies.

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PAX3 Promotes Cell Migration and CXCR4 Gene Expression in Neural Crest Cells

Cited by 9 publications

References 21 publications

From neural border to migratory stage: A comprehensive single cell roadmap of the timing and regulatory logic driving cranial and vagal neural crest emergence

From neural border to migratory stage: A comprehensive single cell roadmap of the timing and regulatory logic driving cranial and vagal neural crest emergence

Ginsenoside Rb1 Modulates the Migration of Bone-Derived Mesenchymal Stem Cells through the SDF-1/CXCR4 Axis and PI3K/Akt Pathway

Cancer stem-like cells of nasopharyngeal carcinoma express CXCR4 and display highly invasive activity

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