Notch ligand Delta-like 1 promotes the metastasis of melanoma by enhancing tumor adhesion

Zhang, J.P.; Li, N.; Bai, Wei; Qiu, Xinyu; Ma, Baoan; Zhou, Yifan; Fan, Qingyu; Li, Shan

doi:10.1590/1414-431x20143368

Cited by 21 publications

(15 citation statements)

References 35 publications

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“…Although HIF-2α was overexpressed under hypoxic conditions, it was found not significantly affect VEGF expression in PCa bone metastasis cell lines in the current study. The adhesion of circulating tumor cells to vascular endothelial cells is one of the key steps for metastasis because it can protect tumor cells from anoikis, fluid shear force, and attack from the immune system [40]. The results of the present study indicated that AHR remarkably suppressed hypoxia-induced heterotypic adhesion between EPCs and PC-3 cells, which implies that the decreased endothelial-PC-3 adhesion may contribute to the abridged angiogenic and metastatic effect exerted by AHR.…”

Section: Pi3k Regulates Hif-1α Signaling and Mediates Hypoxia-inducedsupporting

confidence: 49%

Aromatic Hydrocarbon Receptor Suppresses Prostate Cancer Bone Metastasis Cells-Induced Vasculogenesis of Endothelial Progenitor Cells under Hypoxia

Huang¹,

Guo²,

Jacobi³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Hypoxia leads to the development of neovascularization in solid tumor by regulating VEGF expression. Aromatic hydrocarbon receptor (AHR), a receptor for dioxin-like compounds, functions as a transcription factor through dimerization with hypoxia-inducible factors 1β (HIF-1β) and inhibits the secretion of vascular endothelial growth factor (VEGF). The purpose of this study was to explore whether AHR can suppress hypoxia-induced VEGF production in prostate bone metastasis cells and repress neovascularization in endothelial progenitor cells (EPCs), and, if so, through what mechanisms. Methods: PC-3 or LNCaP cells induced angiogenesis was detected by Matrigel-based tube formation assay, mRNA expression levels was measured by qRT-PCR, VEGF secretion level was determined by ELISA assay, respectively. Results: AHR activation inhibits hypoxia-induced adhesiveness and vasculogenesis of EPCs induced by PC-3 or LNCaP cells under hypoxia. Moreover, AHR activation suppressed hypoxia-induced VEGF production in PC-3 and LNCaP cells (48 ± 14% in PC-3, p = 0.000; 41 ± 14% in LNCaP, p = 0.000) by attenuating HIF-1α and HIF-1β level that in turn diminished the angiogenic ability of EPCs in vitro. Furthermore, we found the mRNA level of hypoxia-inducible factors 1α (HIF-1α) (1.54 ± 0.13 fold in PC-3, p = 0.002, 1.62 ± 0.12 fold in LNCaP, p = 0.001) and HIF-1β (1.67 ± 0.23 fold in PC-3, p = 0.007; 1.75 ± 0.26 fold in LNCaP, p=0.008) were upregulated in prostate cancer bone metastasis PC-3 and LNCaP cell lines in response to hypoxia, and revealed that the regulation of VEGF by HIF-1α and HIF-1β was possibly mediated by the activation of phosphatidylinositol 3-kinase pathway. Conclusion: By providing a mechanistic insight into the modulation of neovascularization by AHR ligand, we suggest that AHR ligand has a strong potential of being a new therapeutic agent with applications in the field of bone metastatic prostate cancer.

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Section: Pi3k Regulates Hif-1α Signaling and Mediates Hypoxia-inducedsupporting

confidence: 49%

Aromatic Hydrocarbon Receptor Suppresses Prostate Cancer Bone Metastasis Cells-Induced Vasculogenesis of Endothelial Progenitor Cells under Hypoxia

Huang¹,

Guo²,

Jacobi³

et al. 2016

Cell Physiol Biochem

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“…DLL1 has been reported to be critical for proliferation in some cancer cells, such as glioma and melanoma cells [23,24]. Thus, we next evaluated the effect of DLL1 downregulation on MCF-7, BT474, and MDA-MB-231 cell growth.…”

Section: Resultsmentioning

confidence: 99%

The Notch ligand DLL1 exerts carcinogenic features in human breast cancer cells

et al. 2019

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Breast cancer (BC) is the most common type of cancer in women and has a high rate of relapse and death. Notch signaling is crucial for normal breast development and homeostasis. Dysregulation of Notch receptors and ligands has been detected in different BC subtypes and shown to be implicated in tumor development, progression, drug resistance, and recurrence. However, the effects of Notch ligands in various types of BC remain poorly understood. In this study, we investigated the effects of the Notch ligand DLL1 in three different human BC cell lines: MCF-7, BT474, and MDA-MB-231. We showed that DLL1 expression is higher in MCF-7 and BT474 than in MDA-MB-231 cells, and that these cells respond differently to DLL1 downregulation. Functional assays in MCF-7 cells demonstrated that siRNA-mediated DLL1 downregulation reduced colony formation efficiency, migration, proliferation, caused cell cycle arrest at the G1 phase, and induced apoptosis. Gene expression studies revealed that these effects in MCF-7 cells were associated with increased expression of the cell cycle arrest p21 gene and decreased expression of genes that promote cell cycle progression (CDK2, SKP2), and survival (BCL2, BIRC5), unravelling possible mechanisms whereby DLL1 downregulation exerts some of its effects. Moreover, our results demonstrate that treatment with recombinant DLL1 increased MCF-7 cell proliferation and migration, confirming that DLL1 contributes to these processes in this BC cell line. DLL1 downregulation reduced the colony formation efficiency of BT474 cells and decreased the migration and invasion abilities of MDA-MB-231 cells but showed no effects in the proliferation and survival of these cells. Conclusions These findings provide further evidence that DLL1 exerts carcinogenic effects in BC cells. The dissimilar effects of DLL1 downregulation observed amongst MCF-7, BT474, and MDA-MB-231 cells is likely due to their distinctive genetic and biologic characteristics, suggesting that DLL1 contributes to BC through various mechanisms.

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“…26 In melanoma, activated Notch signaling enhances the adhesion and metastasis of melanoma cell by up-regulating N-cadherin. 27 On the contrary, inhibition of Notch signaling can promote skin squamous cell carcinoma formation. 28 Similarly, the role of Notch signaling is controversial in HNSCC.…”

Section: Discussionmentioning

confidence: 99%

The Notch signaling pathway in head and neck squamous cell carcinoma: A meta-analysis

Zhao¹,

Yu²,

Xiao³

et al. 2017

Adv Clin Exp Med

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Notch ligand Delta-like 1 promotes the metastasis of melanoma by enhancing tumor adhesion

Cited by 21 publications

References 35 publications

Aromatic Hydrocarbon Receptor Suppresses Prostate Cancer Bone Metastasis Cells-Induced Vasculogenesis of Endothelial Progenitor Cells under Hypoxia

Aromatic Hydrocarbon Receptor Suppresses Prostate Cancer Bone Metastasis Cells-Induced Vasculogenesis of Endothelial Progenitor Cells under Hypoxia

The Notch ligand DLL1 exerts carcinogenic features in human breast cancer cells

The Notch signaling pathway in head and neck squamous cell carcinoma: A meta-analysis

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