Unraveling the function of epithelial-mesenchymal transition (EMT) in colorectal cancer: Metastasis, therapy response, and revisiting molecular pathways

Sabouni, Eisa; Nejad, Melina Maghsodlou; Mojtabavi, Sarah; Khoshduz, Sara; Mojtabavi, Mahsa; Nadafzadeh, Niloufar; Nikpanjeh, Negin; Mirzaei, Sepideh; Hashemi, Mehrdad; Aref, Amir Reza; Khorrami, Ramin; Nabavi, Noushin; Ertaş, Yavuz Nuri; Salimimoghadam, Shokooh; Zandieh, Mohammad Arad; Rahmanian, Parham; Taheriazam, Afshin; Hushmandi, Kiavash

doi:10.1016/j.biopha.2023.114395

Cited by 23 publications

(15 citation statements)

References 244 publications

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“…Previous studies have indicated a strong association between EMT and the ability of cancer cells to invade other tissues and it is a key mechanism contributing to the progression of CRC [ 27 ]. As a high CSRP1 expression was associated with a shorter RFS, next, the relationships between the expression of CSRP1 and mesenchymal markers (SNAI1, SNAI2, ZEB1, ZEB2, TWIST1, TWIST2, and VIM) were studied.…”

Section: Resultsmentioning

confidence: 99%

CSRP1 expression is associated with a mesenchymal, stroma-rich tumor profile and poor prognosis in colon cancer

CANLI

2023

Turkish Journal of Medical Sciences

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Background/aim Cysteine and glycine-rich protein 1 (CSRP1) is involved in the cysteine-rich protein family and is a marker of smooth muscle lineages. In colon cancer, the expression of this gene is associated with poor prognosis. In this study, the aim was to reevaluate its prognostic relationship in independent cohorts and explore potential underlying biological processes that are linked to aggressive behavior in tumors with high CSRP1 expression, such as epithelial-to-mesenchymal transition (EMT), stromal fractions in the tumor microenvironment, and consensus molecular subtypes (CMSs). Materials and methods RNA sequencing (RNAseq)-, microarray-, and single-cell RNAseq (scRNAseq)-based transcriptomic data were obtained from public databases. The EMT score was calculated based on the expression of E-cadherin and vimentin genes using a previously published method. The stromal score generated by the ESTIMATE method was utilized for the analysis of correlation with the CSRP1 expression. The scRNAseq data were analyzed via the Seurat R package. The immunohistochemistry-based protein level expression of CSRP1 was evaluated using the Human Protein Atlas database. Results Lower CSRP1 expression was noted in colon tumors compared to normal colon tissue. Patients with a high CSRP1 expression had shorter recurrence-free, overall, and disease-specific survivals in the GSE39582 and GSE17536 datasets (p < 0.05). The methylation level of the CSRP1 gene was negatively correlated (r = −0.57, p < 0.0001) with CSRP1 expression in The Cancer Genome Atlas colon adenocarcinoma dataset. CSRP1 expression was positively correlated with the expression of mesenchymal markers, EMT score, and stromal score obtained via the ESTIMATE method. CMS4 colon tumors had a significantly higher CSRP1 expression compared to other CMSs. Analysis of the scRNAseq data revealed that CSRP1 was expressed by epithelial cells and cancer-associated fibroblasts in the colorectal tumor microenvironment, which was also confirmed by the protein expression data from the Human Protein Atlas database. Conclusion CSRP1 expression is associated with CMS4, a more mesenchymal stroma-rich molecular profile, and poor prognosis in colon cancer.

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Section: Resultsmentioning

confidence: 99%

CSRP1 expression is associated with a mesenchymal, stroma-rich tumor profile and poor prognosis in colon cancer

CANLI

2023

Turkish Journal of Medical Sciences

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“…In the context of cancer, EMT plays a critical role in tumor progression, particularly in the metastasis process [ 44 ]. EMT enables the separation of cancer cells from the main tumor, infiltration into neighboring tissues, and dissemination to remote locations, ultimately promoting the metastasis of cancer throughout the body [ 45 ]. Additionally, EMT is implicated in therapeutic resistance, as cells undergoing EMT often exhibit increased resistance to chemotherapy and radiation therapy [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

PANoptosis-related molecule CASP2 affects the immune microenvironment and immunotherapy response of hepatocellular carcinoma

Lou,

Chen,

et al. 2024

Heliyon

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“…EMT involved in gastrulation is promoted by the canonical Wnt signaling pathway (38) . EMT participated in metastasis is induced by variety of signaling molecules like Wnt, JAK/STAT3, FGF, EGF BMP, TGFβ, etc (33,39,40) . EMT associated with wound healing is induced by factors such as VEGF and TGFβ (37) .…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA-seq reveals keratinocytes and fibroblasts heterogeneity and their crosstalk via epithelial-mesenchymal transition in psoriasis

Guo

Wang

et al. 2023

Preprint

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As a chronic inflammatory autoimmune skin disease with high global prevalence, the pathogenesis of psoriasis remains inconclusive. We performed a high-resolution single-cell RNA sequencing analysis of 94 759 cells from 13 samples including psoriasis and wide-type mouse model. We presented a comprehensive single-cell transcriptional landscape of the skin immune cells in psoriasis, especially the heterogeneity of keratinocytes and fibroblasts. More interestingly, we discovered that special keratinocyte subtypes and fibroblast subtypes could interact with each other through epithelial–mesenchymal transition and validated the results with drug verification. What’s more, we conducted a tentative exploration of the potential involving pathway and disclosed that the IL-17 signaling pathway may be the most relevant one. Collectively, we revealed the full-cycle landscape of key cells associated with psoriasis and provided a more comprehensive understanding of the pathogenesis of psoriasis.

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Unraveling the function of epithelial-mesenchymal transition (EMT) in colorectal cancer: Metastasis, therapy response, and revisiting molecular pathways

Cited by 23 publications

References 244 publications

CSRP1 expression is associated with a mesenchymal, stroma-rich tumor profile and poor prognosis in colon cancer

CSRP1 expression is associated with a mesenchymal, stroma-rich tumor profile and poor prognosis in colon cancer

PANoptosis-related molecule CASP2 affects the immune microenvironment and immunotherapy response of hepatocellular carcinoma

Single-cell RNA-seq reveals keratinocytes and fibroblasts heterogeneity and their crosstalk via epithelial-mesenchymal transition in psoriasis

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