Collagen XV mediated the epithelial-mesenchymal transition to inhibit hepatocellular carcinoma metastasis

Yao, Ting; Chen, Jinmei; Shen, Leer; Yu, Yijun; Tang, Zisheng; Zang, Guoqing; Zhang, Yi; Chen, Xiaohua

doi:10.21037/jgo-22-299

Cited by 12 publications

(13 citation statements)

References 36 publications

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“…Genes with positive correlation are enriched in associated proteins localized in focal adhesion, cytoskeleton, and endoplasmic reticulum, and participate in cell adhesion (but not cell-cell adhesion) and migration. As expected from literature, we found typical genes that were negatively or positively correlated to the EMT scores, such as Keratin15 (Zhong et al, 2021) or collagen XV (Yao et al, 2022), suggesting that the regulation of their expression level was part of the intra-cellular reorganization that accompanies EMT.…”

Section: Variation Of Gene Expression As Cells Progress Along Emtsupporting

confidence: 86%

Plakins are involved in the maintenance of epithelial polarity

Geay,

Margaron,

Gentien

et al. 2023

Preprint

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As epithelia are the interface between the organism and the external environment, they are often subject to damage and must be frequently renewed. However, maintaining epithelial integrity during this renewal is challenging, and loss of cell polarity is a potent inducer of tumorigenesis. In this study, we used transcriptomic data from breast cancer cells at different stages of tumor development to identify molecular changes associated with the early stages of tumor transformation. We correlated these protein expression profiles with either cell polarity defects or cell progression along the epithelial-to-mesenchymal transition (EMT). We identified plakins, namely epiplakin (EPPK1), desmoplakin (DSP) and periplakin (PPL), that were downregulated in cells that had lost their epithelial polarity and also downregulated in cells that had progressed through EMT. We further tested them experimentally by knocking down their expression in a non-tumorigenic epithelial breast cell line (MCF10A). We demonstrated their causal role in the loss of polarity, as revealed by the misorientation of the nuclear centrosome vector. We also found that vimentin, a marker of EMT, was overexpressed in plakin knocked-down cells, suggesting that plakins may have both a structural and a regulatory role in maintaining the epithelial state.

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Section: Variation Of Gene Expression As Cells Progress Along Emtsupporting

confidence: 86%

Plakins are involved in the maintenance of epithelial polarity

Geay,

Margaron,

Gentien

et al. 2023

Preprint

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“…The western blotting showed an increase in the level of a representative epithelial marker, Ecadherin, and the downregulation of several EMT markers, i.e., N-cadherin, vimentin, and snail1 (but not ZEB2) (Figure 2F). Enhancement of cancer cell growth, migration, and invasion activities can be caused by EMT events (19,20). Therefore, we examined these cellular activities in MDA-MutZEB1.…”

Section: Establishment Of a Subline Of Mutzeb1overexpressing Cellsmentioning

confidence: 99%

LOXL1 and LOXL4 are novel target genes of the Zn2+-bound form of ZEB1 and play a crucial role in the acceleration of invasive events in triple-negative breast cancer cells

Hirabayashi

Maruyama²,

Tomonobu³

et al. 2023

Front. Oncol.

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BackgroundEMT has been proposed to be a crucial early event in cancer metastasis. EMT is rigidly regulated by the action of several EMT-core transcription factors, particularly ZEB1. We previously revealed an unusual role of ZEB1 in the S100A8/A9-mediated metastasis in breast cancer cells that expressed ZEB1 at a significant level and showed that the ZEB1 was activated on the MCAM-downstream pathway upon S100A8/A9 binding. ZEB1 is well known to require Zn2+ for its activation based on the presence of several Zn-finger motifs in the transcription factor. However, how Zn2+-binding works on the pleiotropic role of ZEB1 through cancer progression has not been fully elucidated.MethodsWe established the engineered cells, MDA-MB-231 MutZEB1 (MDA-MutZEB1), that stably express MutZEB1 (ΔZn). The cells were then evaluated in vitro for their invasion activities. Finally, an RNA-Seq analysis was performed to compare the gene alteration profiles of the established cells comprehensively.ResultsMDA-MutZEB1 showed a significant loss of the EMT, ultimately stalling the invasion. Inclusive analysis of the transcription changes after the expression of MutZEB1 (ΔZn) in MDA-MB-231 cells revealed the significant downregulation of LOX family genes, which are known to play a critical role in cancer metastasis. We found that LOXL1 and LOXL4 remarkably enhanced cancer invasiveness among the LOX family genes with altered expression.ConclusionsThese findings indicate that ZEB1 potentiates Zn2+-mediated transcription of plural EMT-relevant factors, including LOXL1 and LOXL4, whose upregulation plays a critical role in the invasive dissemination of breast cancer cells.

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“…Upregulation of the nitric oxide synthase trafficker NOSTRIN in venous-like and capillary-like cells compared to the rest of ECs ( Fig 2E ) suggests that eNOS is preferentially located away from the membrane, with important consequences for hemostasis, vasoreactivity, and inflammation. In addition, the abundance of EPB41L3 and COL15A1 in venous ECs suggests a low predisposition for endothelial-mesenchymal transformation due to SNAI1 inhibition ( S3C Fig ) [ 39 , 40 ].…”

Section: Resultsmentioning

confidence: 99%

The intricate cellular ecosystem of human peripheral veins as revealed by single-cell transcriptomic analysis

Rojas,

Zigmond,

Pereira-Simon

et al. 2024

PLoS ONE

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The venous system has been historically understudied despite its critical roles in blood distribution, heart function, and systemic immunity. This study dissects the microanatomy of upper arm veins at the single cell level, and how it relates to wall structure, remodeling processes, and inflammatory responses to injury. We applied single-cell RNA sequencing to 4 non-diseased human veins (3 basilic, 1 cephalic) obtained from organ donors, followed by bioinformatic and histological analyses. Unsupervised clustering of 20,006 cells revealed a complex ecosystem of endothelial cell (EC) types, smooth muscle cell (SMCs) and pericytes, various types of fibroblasts, and immune cell populations. The venous endothelium showed significant upregulation of cell adhesion genes, with arteriovenous zonation EC phenotypes highlighting the heterogeneity of vasa vasorum (VV) microvessels. Venous SMCs had atypical contractile phenotypes and showed widespread localization in the intima and media. MYH11+DESlo SMCs were transcriptionally associated with negative regulation of contraction and pro-inflammatory gene expression. MYH11+DEShi SMCs showed significant upregulation of extracellular matrix genes and pro-migratory mediators. Venous fibroblasts ranging from secretory to myofibroblastic phenotypes were 4X more abundant than SMCs and widely distributed throughout the wall. Fibroblast-derived angiopoietin-like factors were identified as versatile signaling hubs to regulate angiogenesis and SMC proliferation. An abundant monocyte/macrophage population was detected and confirmed by histology, including pro-inflammatory and homeostatic phenotypes, with cell counts positively correlated with age. Ligand-receptor interactome networks identified the venous endothelium in the main lumen and the VV as a niche for monocyte recruitment and infiltration. This study underscores the transcriptional uniqueness of venous cells and their relevance for vascular inflammation and remodeling processes. Findings from this study may be relevant for molecular investigations of upper arm veins used for vascular access creation, where single-cell analyses of cell composition and phenotypes are currently lacking.

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Collagen XV mediated the epithelial-mesenchymal transition to inhibit hepatocellular carcinoma metastasis

Cited by 12 publications

References 36 publications

Plakins are involved in the maintenance of epithelial polarity

Plakins are involved in the maintenance of epithelial polarity

LOXL1 and LOXL4 are novel target genes of the Zn2+-bound form of ZEB1 and play a crucial role in the acceleration of invasive events in triple-negative breast cancer cells

The intricate cellular ecosystem of human peripheral veins as revealed by single-cell transcriptomic analysis

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