From shape-shifting embryonic cells to oncology: The fascinating history of epithelial mesenchymal transition

Akhurst, Rosemary J.

doi:10.1016/j.semcancer.2023.10.003

Cited by 11 publications

(3 citation statements)

References 185 publications

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“…Epithelial-mesenchymal transition (EMT) refers to the changes that occur in cells under certain physiological and pathological conditions. EMT plays an important role in cell embryonic development, organ differentiation, wound healing, and tumor metastasis [ 29 ]. Invasion and metastasis of pancreatic cancer are closely related to EMT [ 30 – 33 ].…”

Section: Discussionmentioning

confidence: 99%

HHLA2 deficiency inhibits pancreatic cancer progression and THP-1 macrophage M2 polarization via EGFR/MAPK/ERK and mTOR/AKT pathway

Zhou,

Wang,

Zhao

et al. 2024

World J Surg Onc

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Background Human endogenous retrovirus subfamily H long terminal repeat associating protein 2, (HHLA2), a member of B7 family, exhibits heightened expression in various malignant tumors. However, the exact functions of HHLA2 in pancreatic cancer (PC) remain incompletely elucidated. Methods We initially conducted an analysis of the B7 family members’ expression pattern in pancreatic tumor samples and adjacent normal tissues using The Cancer Genome Atlas (TCGA) database. Subsequently, immunohistochemistry, RT-qPCR and western blot methods were used to assess HHLA2 expression levels in PC tissues and cell lines. Furthermore, after silencing HHLA2 in PC cell lines, cell migration and proliferation of PC cells were detected by wound healing and CCK-8 assays, and cell invasion of PC cells was detected by transwell assays. We also investigated the regulation of epithelial-mesenchymal transition (EMT) markers and levels of EGFR, MEK, ERK1/2, mTOR and AKT via western blot analysis. Finally, the correlation between HHLA2 expression and immune infiltration was further explored. Results Silencing of HHLA2 resulted in the inhibition of PC cell proliferation, migration and invasion, potentially through the suppression of the EGFR/MAPK/ERK and mTOR/AKT signaling pathway. Additionally, silencing HHLA2 led to the inhibition of M2-type polarization of tumor associated macrophages (TAMs). Conclusion The knockdown of HHLA2 was observed to inhibit the migration and invasion of PC cells through the regulation of the EMT process and EGFR/MAPK/ERK and mTOR/AKT pathway. Furthermore, silencing HHLA2 was found to modulate M2 polarization of TAMs. These finding suggest that HHLA2 could be a promising therapeutic target for Pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

HHLA2 deficiency inhibits pancreatic cancer progression and THP-1 macrophage M2 polarization via EGFR/MAPK/ERK and mTOR/AKT pathway

Zhou,

Wang,

Zhao

et al. 2024

World J Surg Onc

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“…Normally, EMT is a process in which the transient appearance of mesenchymal cells contributes to normal wound healing. In addition to this role, EMT is involved in embryogenesis and oncogenesis [ 52 ], and various pathological settings characterized by fibrosis. In fact, EMT becomes harmful when the dysregulation of the repair mechanisms, triggered by chronic inflammation and sustained by factors like TGF-β, EGF, FGF, PDGF, and IGF-1, results in the persistent loss of typical epithelial features.…”

Section: The Role Of Immune Dysregulation In Driving Epithelial-to-me...mentioning

confidence: 99%

Intestinal Fibrogenesis in Inflammatory Bowel Diseases: Exploring the Potential Role of Gut Microbiota Metabolites as Modulators

Cicchinelli,

Gemma,

Pignataro

et al. 2024

Pharmaceuticals

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Fibrosis, sustained by the transformation of intestinal epithelial cells into fibroblasts (epithelial-to-mesenchymal transition, EMT), has been extensively studied in recent decades, with the molecular basis well-documented in various diseases, including inflammatory bowel diseases (IBDs). However, the factors influencing these pathways remain unclear. In recent years, the role of the gut microbiota in health and disease has garnered significant attention. Evidence suggests that an imbalanced or dysregulated microbiota, along with environmental and genetic factors, may contribute to the development of IBDs. Notably, microbes produce various metabolites that interact with host receptors and associated signaling pathways, influencing physiological and pathological changes. This review aims to present recent evidence highlighting the emerging role of the most studied metabolites as potential modulators of molecular pathways implicated in intestinal fibrosis and EMT in IBDs. These studies provide a deeper understanding of intestinal inflammation and fibrosis, elucidating the molecular basis of the microbiota role in IBDs, paving the way for future treatments.

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“…However, during carcinogenic rewiring these correlations were lost, replaced by Sox9 (r = 0.67), as well as other important drivers of cancer phenotypes including Tgfb1 (r = 0.60) (table S1). Tgfb1 is a growth factor known to play multiple roles in tumor development, acting as a growth inhibitor at early stages and switching roles to become an inducer of the epithelial-mesenchymal transition during tumor progression (39). It is also a major mediator of immunosuppression that, when inhibited with blocking antibodies, improves immunotherapy outcomes in mouse models (40,41).…”

Section: Rewiring Of Stem Cell Gene Expression Network In Tumorsmentioning

confidence: 99%

Stem-cell states converge in multistage cutaneous squamous cell carcinoma development

Taylor,

Kandyba,

Halliwill

et al. 2024

Science

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Stem cells play a critical role in cancer development by contributing to cell heterogeneity, lineage plasticity, and drug resistance. We created gene expression networks from hundreds of mouse tissue samples (both normal and tumor) and integrated these with lineage tracing and single-cell RNA-seq, to identify convergence of cell states in premalignant tumor cells expressing markers of lineage plasticity and drug resistance. Two of these cell states representing multilineage plasticity or proliferation were inversely correlated, suggesting a mutually exclusive relationship. Treatment of carcinomas in vivo with chemotherapy repressed the proliferative state and activated multilineage plasticity whereas inhibition of differentiation repressed plasticity and potentiated responses to cell cycle inhibitors. Manipulation of this cell state transition point may provide a source of potential combinatorial targets for cancer therapy.

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From shape-shifting embryonic cells to oncology: The fascinating history of epithelial mesenchymal transition

Cited by 11 publications

References 185 publications

HHLA2 deficiency inhibits pancreatic cancer progression and THP-1 macrophage M2 polarization via EGFR/MAPK/ERK and mTOR/AKT pathway

HHLA2 deficiency inhibits pancreatic cancer progression and THP-1 macrophage M2 polarization via EGFR/MAPK/ERK and mTOR/AKT pathway

Intestinal Fibrogenesis in Inflammatory Bowel Diseases: Exploring the Potential Role of Gut Microbiota Metabolites as Modulators

Stem-cell states converge in multistage cutaneous squamous cell carcinoma development

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