Editorial: Molecular Mechanisms and Signaling in Endothelial Cell Biology and Vascular Heterogeneity

Ren, Bin; Ramchandran, Ramani; Yang, Xiaofeng

doi:10.3389/fcell.2021.821100

Cited by 2 publications

(2 citation statements)

References 51 publications

(54 reference statements)

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“…Finally, this study validated previous results [ 17 ] indicating that pNET CSCs could move toward the vascular niches, in which vascular ECs are a key player. Given the critical role of ECs in arteriolar differentiation and tumor progression [ 15 , 16 , 17 , 83 , 84 , 85 ], vascular ECs in highly vascularized pNETs may nurture CSCs by direct EC-CSC interactions and by indirect generation of such vascular niche factors as LPA to activate PKD1 signaling [ 4 , 16 , 17 , 24 , 28 ], thereby, leading to progression toward malignancy, drug resistance and metastasis. Based upon previous studies and this study, we propose a working model ( Figure 7 ).…”

Section: Discussionmentioning

confidence: 99%

Protein Kinase D1 Signaling in Cancer Stem Cells with Epithelial-Mesenchymal Plasticity

Guo

Jiang

Rose

et al. 2022

Cells

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Pancreatic neuroendocrine tumors (pNETs) are extremely diverse and highly vascularized neoplasms that arise from endocrine cells in the pancreas. The pNETs harbor a subpopulation of stem cell-like malignant cells, known as cancer stem cells (CSCs), which contribute to intratumoral heterogeneity and promote tumor maintenance and recurrence. In this study, we demonstrate that CSCs in human pNETs co-express protein kinase PKD1 and CD44. We further identify PKD1 signaling as a critical pathway in the control of CSC maintenance in pNET cells. PKD1 signaling regulates the expression of a CSC- and EMT-related gene signature and promotes CSC self-renewal, likely leading to the preservation of a subpopulation of CSCs at an intermediate EMT state. This suggests that the PKD1 signaling pathway may be required for the development of a unique CSC phenotype with plasticity and partial EMT. Given that the signaling networks connected with CSC maintenance and EMT are complex, and extend through multiple levels of regulation, this study provides insight into signaling regulation of CSC plasticity and partial EMT in determining the fate of CSCs. Inhibition of the PKD1 pathway may facilitate the elimination of specific CSC subsets, thereby curbing tumor progression and metastasis.

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Section: Discussionmentioning

confidence: 99%

Protein Kinase D1 Signaling in Cancer Stem Cells with Epithelial-Mesenchymal Plasticity

Guo

Jiang

Rose

et al. 2022

Cells

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“…Finally, similar to our recent study [24], pNET CSCs could move toward the vascular niches, in which vascular ECs are a key player. Given the critical role of ECs in arteriolar differentiation and tumor progression [8,10,24,[77][78][79], ECs in highly vascularized pNETs may nurture CSCs by direct interactions and indirect generation of such vascular niche factors as LPA, likely via communication with the PKD-1 [6,8,18,24], thereby leading to progression toward malignancy, drug resistance and metastasis. (Figure 6).…”

Section: Discussionmentioning

confidence: 99%

PKD-1 Signaling Is Required for the Maintenance of CSCs with Epithelial-mesenchymal Plasticity in Pancreatic Neuroendocrine Tumors

Guo

Jiang

Rose

et al. 2022

Preprint

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Pancreatic neuroendocrine tumors (pNETs) are extremely heterogeneous and highly vascularized neoplasms that arise from endocrine cells in the pancreas. pNETs harbor a subpopulation of stem cell-like cancer cells (cancer stem cells/CSCs), which contribute to intratumoral heterogeneity and promote tumor maintenance and recurrence. In this study we demonstrated that CSCs in human pNETs co-expressed PKD-1 and CD44. We further identified PKD-1 signaling as a critical pathway in the regulation of CSC maintenance in pNET cells. PKD-1 signaling regulated the expression of a CSC-related gene signature and promoted CSC self-renewal. Intriguingly, pharmacological or genetic disruption of PKD-1 signaling in human pNET cells impaired lysophosphatidic acid-induced expression of genes associated with epithelial to mesenchymal transition (EMT), specifically E-cadherin and vimentin. This study indicates that PKD-1 signaling is essential for the maintenance of a subpopulation of CSCs in pNETs at an intermediate state along the epithelial to mesenchymal spectrum, thereby leading to a CSC phenotype with plasticity and partial EMT. Inhibiting the PKD-1 pathway may facilitate the elimination of CSC subpopulations to curb pNET progression, therapeutic resistance and metastasis. Given that the signaling networks associated with CSC maintenance and EMT are complex and extend across multiple levels of gene regulation, this study provides insight into signaling regulation of partial EMT in determining CSC fate and aids in developing potential therapeutic strategies that target different subsets of CSCs in a variety of cancers.

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Editorial: Molecular Mechanisms and Signaling in Endothelial Cell Biology and Vascular Heterogeneity

Cited by 2 publications

References 51 publications

Protein Kinase D1 Signaling in Cancer Stem Cells with Epithelial-Mesenchymal Plasticity

Protein Kinase D1 Signaling in Cancer Stem Cells with Epithelial-Mesenchymal Plasticity

PKD-1 Signaling Is Required for the Maintenance of CSCs with Epithelial-mesenchymal Plasticity in Pancreatic Neuroendocrine Tumors

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