Dataset Information

Multi-Omics Characterization of the Spontaneous Mesenchymal-Epithelial Transition in the PMC42 Breast Cancer Cell Lines.

ABSTRACT: Epithelial-mesenchymal plasticity (EMP), encompassing epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET), are considered critical events for cancer metastasis. We investigated chromosomal heterogeneity and chromosomal instability (CIN) profiles of two sister PMC42 breast cancer (BC) cell lines to assess the relationship between their karyotypes and EMP phenotypic plasticity. Karyotyping by GTG banding and exome sequencing were aligned with SWATH quantitative proteomics and existing RNA-sequencing data from the two PMC42 cell lines; the mesenchymal, parental PMC42-ET cell line and the spontaneously epithelially shifted PMC42-LA daughter cell line. These morphologically distinct PMC42 cell lines were also compared with five other BC cell lines (MDA-MB-231, SUM-159, T47D, MCF-7 and MDA-MB-468) for their expression of EMP and cell surface markers, and stemness and metabolic profiles. The findings suggest that the epithelially shifted cell line has a significantly altered ploidy of chromosomes 3 and 13, which is reflected in their transcriptomic and proteomic expression profiles. Loss of the TGF?R2 gene from chromosome 3 in the epithelial daughter cell line inhibits its EMT induction by TGF-? stimulus. Thus, integrative 'omics' characterization established that the PMC42 system is a relevant MET model and provides insights into the regulation of phenotypic plasticity in breast cancer.

SUBMITTER: Bhatia S

PROVIDER: S-EPMC6723942 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Multi-Omics Characterization of the Spontaneous Mesenchymal-Epithelial Transition in the PMC42 Breast Cancer Cell Lines.

Bhatia Sugandha S Monkman James J Blick Tony T Duijf Pascal Hg PH Nagaraj Shivashankar H SH Thompson Erik W EW

Journal of clinical medicine 20190819 8

Epithelial-mesenchymal plasticity (EMP), encompassing epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET), are considered critical events for cancer metastasis. We investigated chromosomal heterogeneity and chromosomal instability (CIN) profiles of two sister PMC42 breast cancer (BC) cell lines to assess the relationship between their karyotypes and EMP phenotypic plasticity. Karyotyping by GTG banding and exome sequencing were aligned with SWATH quantitative prot ...[more]

PMID: 31430931

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Project description:Metabolic rewiring has been recognized as an important feature to the progression of cancer. However, the essential components and functions of lipid metabolic networks in breast cancer progression are not fully understood. In this study, we investigated the roles of altered lipid metabolism in the malignant phenotype of breast cancer. Using a spheroid-induced epithelial-mesenchymal transition (EMT) model, we conducted multi-layered lipidomic and transcriptomic analysis to comprehensively describe the rewiring of the breast cancer lipidome during the malignant transformation. A tremendous homeostatic disturbance of various complex lipid species including ceramide, sphingomyelin, ether-linked phosphatidylcholines, and ether-linked phosphatidylethanolamine was found in the mesenchymal state of cancer cells. Noticeably, polyunsaturated fatty acids composition in spheroid cells was significantly decreased, accordingly with the gene expression patterns observed in the transcriptomic analysis of associated regulators. For instance, the up-regulation of SCD, ACOX3, and FADS1 and the down-regulation of PTPLB, PECR, and ELOVL2 were found among other lipid metabolic regulators. Significantly, the ratio of C22:6n3 (docosahexaenoic acid, DHA) to C22:5n3 was dramatically reduced in spheroid cells analogously to the down-regulation of ELOVL2. Following mechanistic study confirmed the up-regulation of SCD and down-regulation of PTPLB, PECR, ELOVL2, and ELOVL3 in the spheroid cells. Furthermore, the depletion of ELOVL2 induced metastatic characteristics in breast cancer cells via the SREBPs axis. A subsequent large-scale analysis using 51 breast cancer cell lines demonstrated the reduced expression of ELOVL2 in basal-like phenotypes. Breast cancer patients with low ELOVL2 expression exhibited poor prognoses (HR = 0.76, CI = 0.67-0.86). Collectively, ELOVL2 expression is associated with the malignant phenotypes and appear to be a novel prognostic biomarker in breast cancer. In conclusion, the present study demonstrates that there is a global alteration of the lipid composition during EMT and suggests the down-regulation of ELOVL2 induces lipid metabolism reprogramming in breast cancer and contributes to their malignant phenotypes.

Dataset Information

Multi-Omics Characterization of the Spontaneous Mesenchymal-Epithelial Transition in the PMC42 Breast Cancer Cell Lines.

Publications

Multi-Omics Characterization of the Spontaneous Mesenchymal-Epithelial Transition in the PMC42 Breast Cancer Cell Lines.

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