Similar Datasets
Project description:Loss of MLL3 facilitates mesenchymal cells to acquire a mesenchymal/epithelial hybrid state during metastatic colonization. The MET occurring in distant metastases is likely driven by stromal signals in the metastatic niche. One signaling pathway that promotes the MET is the activation of protein kinase A (PKA). The MET hybrid cells can be identified as CD44+CD104+/high. Forskolin treatment generated significantly more CD44+CD104high hybrid cells in MLL3-mutant cells than the WT MDA-MB-231 cells. While both WT and MLL3-mutant CD44+CD104high hybrid EMT cells showed significantly increased lung metastatic ability than the counterpart CD44+CD104low mesenchymal cells, the MLL3-mutant hybrid cells showed a much greater metastasis-initiating ability than the WT hybrid cells. Here we reported the gene expression profiles of CD44+CD104high E/M hybird and CD44+CD104-/low mesenchymal cell populations sorted from Foskolin-treated, MLL3-null MDA-MB-231 cells.
2022-10-07 | GSE171444 | GEO
Project description:Phenotypic plasticity associated with the hybrid epithelial-mesenchymal transition (EMT) state is crucial to metastatic seeding and outgrowth. We showed that deletion of the epigenetic regulator MLL3, a tumor suppressor frequently altered in human cancer, promoted the acquisition of the hybrid EMT state in both epithelial and mesenchymal breast cancer cells by facilitating EMT and MET, distinct from other known EMT regulators mediating unidirectional changes. MLL3 deletion greatly increased metastasis by enhancing metastatic outgrowth during colonization. Mechanistically, MLL3 loss led to IFNγ signaling upregulation, which contributes to the induction of hybrid EMT cells and the enhanced metastatic capacity.
2022-10-07 | GSE206658 | GEO
Project description:Phenotypic plasticity associated with the hybrid epithelial-mesenchymal transition (EMT) state is crucial to metastatic seeding and outgrowth. However, the mechanisms controlling the induction of hybrid EMT remain poorly defined. We showed that deletion of the epigenetic regulator MLL3, a tumor suppressor frequently altered in human cancer, promoted the acquisition of the hybrid EMT state in both epithelial and mesenchymal breast cancer cells by facilitating EMT and MET, distinct from other known EMT regulators mediating unidirectional changes. Consequently, MLL3 deletion greatly increased metastasis by enhancing metastatic outgrowth during colonization. Mechanistically, MLL3 loss led to IFNγ signaling upregulation, which contributes to the induction of hybrid EMT cells and the enhanced metastatic capacity.
2022-10-07 | GSE206656 | GEO
Project description:Loss of MLL3 facilitates mesenchymal cells to acquire a mesenchymal/epithelial hybrid state during metastatic colonization. The MET occurring in distant metastases is likely driven by stromal signals in the metastatic niche. One signaling pathway that promotes the MET is the activation of protein kinase A (PKA). The MET hybrid cells can be identified as CD44+CD104+/high. Forskolin treatment generated significantly more CD44+CD104high hybrid cells in MLL3-mutant cells than the WT MDA-MB-231 cells. While both WT and MLL3-mutant CD44+CD104high hybrid EMT cells showed significantly increased lung metastatic ability than the counterpart CD44+CD104low mesenchymal cells, the MLL3-mutant hybrid cells showed a much greater metastasis-initiating ability than the WT hybrid cells. Here we reported the gene expression profiles of CD44+CD104high E/M hybird and CD44+CD104-/low mesenchymal cell populations sorted from Foskolin-treated, WT MDA-MB-231 cells.
2022-10-07 | GSE206653 | GEO
Project description:Phenotypic plasticity associated with the hybrid epithelial-mesenchymal transition (EMT) state is crucial to metastatic seeding and outgrowth. However, the mechanisms controlling the induction of hybrid EMT remain poorly defined. We showed that deletion of the epigenetic regulator MLL3, a tumor suppressor frequently altered in human cancer, promoted the acquisition of the hybrid EMT state in both epithelial and mesenchymal breast cancer cells by facilitating EMT and MET, distinct from other known EMT regulators mediating unidirectional changes. Consequently, MLL3 deletion greatly increased metastasis by enhancing metastatic outgrowth during colonization. Mechanistically, MLL3 loss led to IFNγ signaling upregulation, which contributes to the induction of hybrid EMT cells and the enhanced metastatic capacity.
2022-10-07 | GSE206657 | GEO
Project description:Loss of MLL3 facilitates mesenchymal cells to acquire a mesenchymal/epithelial hybrid state during metastatic colonization. MLL3 loss led to IFNg signaling upregulation, which contributes to the induction of hybrid EMT cells and the enhanced metastatic capacity. Here we reported the gene expression profiles of WT and MLL3-KO MDA-MB-231 cells.
2022-10-07 | GSE206655 | GEO
Project description:FAT1, a protocadherin, is among the most frequently mutated genes in human cancers1-5. However, the role and the molecular mechanisms by which FAT1 mutations control tumour initiation and progression are poorly understood. In the present study we used different mouse cancer models including skin squamous cell carcinoma (SCC) and lung tumours we found that Fat1 deletion accelerated tumour initiation and malignant progression and promoted hybrid epithelial to mesenchymal transition (EMT) phenotype. This hybrid EMT state was also found in FAT1 mutated human SCCs. Fat1 deleted skin SCCs presented increased tumour stemness and spontaneous metastasis. Transcriptional and chromatin profiling revealed that Yap1 and Sox2 are involved in promoting and stabilizing hybrid EMT state. To unravel the molecular mechanisms by which FAT1 (a protein located on the plasma membrane), lead to the transcriptional changes, we performed phosphor-proteomic analysis of A388 FAT1 WT human SCC cell lines and A388 FAR1 CRISPR KO. This analysis revealed that FAT1 loss of function activates a CAMK2/CD44/SRC axis that promotes YAP/ZEB1 nuclear translocation and stimulates the mesenchymal state, as well as a CAMK2-EZH2 axis that promotes activation of SOX2, which sustains the epithelial state. This comprehensive analysis also identified drug resistance and vulnerabilities in FAT1 deficient tumours with important implications for cancer therapy. Altogether, our studies revealed that Fat1 loss of function promotes tumour initiation, progression, invasiveness, stemness and metastasis through the induction of a hybrid EMT state.
2021-01-18 | PXD022268 | Pride
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-12-04 | GSE158506 | GEO
Project description:FAT1, a protocadherin, is among the most frequently mutated genes in human cancers. However, the role and the molecular mechanisms by which FAT1 mutations control tumor initiation and progression are poorly understood. Here, using different mouse cancer models including skin squamous cell carcinoma (SCC) and lung tumors we found that Fat1 deletion accelerated tumor initiation and malignant progression and promoted hybrid epithelial to mesenchymal transition (EMT) phenotype. This hybrid EMT state was also found in FAT1 mutated human SCCs. Fat1 deleted skin SCCs presented increased tumor stemness and spontaneous metastasis. Transcriptional and chromatin profiling combined with proteomic analyses and mechanistic studies revealed that FAT1 loss of function activates a CAMK2/CD44/SRC axis that promotes YAP/ZEB1 nuclear translocation and stimulates the mesenchymal state, as well as a CAMK2-EZH2 axis that promotes activation of SOX2, which sustains the epithelial state. This comprehensive analysis also identified drug resistance and vulnerabilities in FAT1 deficient tumors with important implications for cancer therapy. Altogether, our studies revealed that Fat1 loss of function promotes tumor initiation, progression, invasiveness, stemness and metastasis through the induction of a hybrid EMT state.
2020-12-04 | GSE158503 | GEO
Project description:FAT1, a protocadherin, is among the most frequently mutated genes in human cancers. However, the role and the molecular mechanisms by which FAT1 mutations control tumor initiation and progression are poorly understood. Here, using different mouse cancer models including skin squamous cell carcinoma (SCC) and lung tumors we found that Fat1 deletion accelerated tumor initiation and malignant progression and promoted hybrid epithelial to mesenchymal transition (EMT) phenotype. This hybrid EMT state was also found in FAT1 mutated human SCCs. Fat1 deleted skin SCCs presented increased tumor stemness and spontaneous metastasis. Transcriptional and chromatin profiling combined with proteomic analyses and mechanistic studies revealed that FAT1 loss of function activates a CAMK2/CD44/SRC axis that promotes YAP/ZEB1 nuclear translocation and stimulates the mesenchymal state, as well as a CAMK2-EZH2 axis that promotes activation of SOX2, which sustains the epithelial state. This comprehensive analysis also identified drug resistance and vulnerabilities in FAT1 deficient tumors with important implications for cancer therapy. Altogether, our studies revealed that Fat1 loss of function promotes tumor initiation, progression, invasiveness, stemness and metastasis through the induction of a hybrid EMT state.
2020-12-04 | GSE158505 | GEO