Notch signaling regulates vessel structure and function via Hspg2

Zhao, Xiaohu; Zhang, Tongmei; Yan, Yi-Shang; Liu, Fengzhou; Li, Chengfei; Fan, Jieyi; Pan, Yikai; Li, Xi; Wang, Yongchun

doi:10.1016/j.gene.2022.146439

Cited by 2 publications

(2 citation statements)

References 33 publications

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“…For tip cells, we observed high expression levels of the genes COL4A1 and COL4A2 , which are correlated with a pro‐tumourigenic environment and promote hepatocarcinogenesis 41 . Simultaneously, increased NOTCH4 and HSPG2 signals were detected, which contribute to tumour vascular structure formation 42 . For lymphatic cells, upregulation of PHGR1 and TFF3 was observed, which is essential for the invasion and metastasis of colorectal cancer 43,44 .…”

Section: Resultsmentioning

confidence: 88%

“… 41 Simultaneously, increased NOTCH4 and HSPG2 signals were detected, which contribute to tumour vascular structure formation. 42 For lymphatic cells, upregulation of PHGR1 and TFF3 was observed, which is essential for the invasion and metastasis of colorectal cancer. 43 , 44 Notably, high expression of NOTCH4 and HSPG2 in tip cells were associated with poor prognosis of MCA patients (Figure 6G ).…”

Section: Resultsmentioning

confidence: 99%

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Integrating single‐cell and spatial analysis reveals MUC1‐mediated cellular crosstalk in mucinous colorectal adenocarcinoma

Zhou,

Shen,

Zheng

et al. 2024

Clinical & Translational Med

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BackgroundMucinous colorectal adenocarcinoma (MCA) is a distinct subtype of colorectal cancer (CRC) with the most aggressive pattern, but effective treatment of MCA remains a challenge due to its vague pathological characteristics. An in‐depth understanding of transcriptional dynamics at the cellular level is critical for developing specialised MCA treatment strategies.MethodsWe integrated single‐cell RNA sequencing and spatial transcriptomics data to systematically profile the MCA tumor microenvironment (TME), particularly the interactome of stromal and immune cells. In addition, a three‐dimensional bioprinting technique, canonical ex vivo co‐culture system, and immunofluorescence staining were further applied to validate the cellular communication networks within the TME.ResultsThis study identified the crucial intercellular interactions that engaged in MCA pathogenesis. We found the increased infiltration of FGF7+/THBS1+ myofibroblasts in MCA tissues with decreased expression of genes associated with leukocyte‐mediated immunity and T cell activation, suggesting a crucial role of these cells in regulating the immunosuppressive TME. In addition, MS4A4A+ macrophages that exhibit M2‐phenotype were enriched in the tumoral niche and high expression of MS4A4A+ was associated with poor prognosis in the cohort data. The ligand‐receptor‐based intercellular communication analysis revealed the tight interaction of MUC1+ malignant cells and ZEB1+ endothelial cells, providing mechanistic information for MCA angiogenesis and molecular targets for subsequent translational applications.ConclusionsOur study provides novel insights into communications among tumour cells with stromal and immune cells that are significantly enriched in the TME during MCA progression, presenting potential prognostic biomarkers and therapeutic strategies for MCA.Key points Tumour microenvironment profiling of MCA is developed. MUC1+ tumour cells interplay with FGF7+/THBS1+ myofibroblasts to promote MCA development. MS4A4A+ macrophages exhibit M2 phenotype in MCA. ZEB1+ endotheliocytes engage in EndMT process in MCA.

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Section: Resultsmentioning

confidence: 88%

Section: Resultsmentioning

confidence: 99%

Integrating single‐cell and spatial analysis reveals MUC1‐mediated cellular crosstalk in mucinous colorectal adenocarcinoma

Zhou,

Shen,

Zheng

et al. 2024

Clinical & Translational Med

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Investigation of the correlation between AGRN expression and perineural invasion in colon cancer

Chen,

Zhang,

Gao

et al. 2024

Front. Mol. Biosci.

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Background and PurposeColon cancer is one of the most common gastrointestinal malignancies. According to the traditional view, the primary modes of transmission include direct dissemination, hematogenous metastasis, and lymph node metastasis. In recent years, the role of perineural invasion (PNI) in the spread and metastasis of tumors has received immense attention. However, there are still relatively few reports on the potential mechanisms and biomarkers of PNI occurrence and development in colon cancer.MethodWe identified genes linked to the onset and progression of PNI in colon cancer using bioinformatics tools and extensive databases. Gene function enrichment analysis was used to explore the potential roles of these genes in tumor proliferation, invasion, and PNI. A collection of postoperative pathological specimens from colon cancer patients who underwent surgery, related clinicopathological data, and immunohistochemistry were used to validate AGRN expression in PNI tissues.ResultsBioinformatics analysis revealed that AGRN is overexpressed in colon cancer tissues and correlates with poor patient prognosis. The findings from gene association and enrichment studies indicate that AGRN and its associated genes may play a role in PNI development and progression in colon cancer by simultaneously enhancing tumor cell invasion and neural cell growth. Immunohistochemical analysis of clinical samples confirmed that AGRN expression is elevated in colon cancer tissues with PNI.ConclusionWe found that AGRN is significantly overexpressed in colon cancer tissues exhibiting PNI and is linked to poor patient survival. AGRN and its related genes may contribute to PNI by promoting tumor cell invasion and neural cell growth. Hence, AGRN may play a crucial role in the initiation and progression of PNI in colon cancer.

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Notch signaling regulates vessel structure and function via Hspg2

Cited by 2 publications

References 33 publications

Integrating single‐cell and spatial analysis reveals MUC1‐mediated cellular crosstalk in mucinous colorectal adenocarcinoma

Integrating single‐cell and spatial analysis reveals MUC1‐mediated cellular crosstalk in mucinous colorectal adenocarcinoma

Investigation of the correlation between AGRN expression and perineural invasion in colon cancer

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