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Deciphering Hydrodynamic and Drug-Resistant Behaviors of Metastatic EMT Breast Cancer Cells Moving in a Constricted Microcapillary
Open AccessArticle

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

1
Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059, Australia
2
School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD 4000, Australia
3
Translational Research Institute, Brisbane, QLD 4102, Australia
4
University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia
*
Authors to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(8), 1253; https://doi.org/10.3390/jcm8081253
Received: 10 July 2019 / Revised: 15 August 2019 / Accepted: 15 August 2019 / Published: 19 August 2019
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 TGFβR2 gene from chromosome 3 in the epithelial daughter cell line inhibits its EMT induction by TGF-β 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. View Full-Text
Keywords: copy number variations (CNV); epithelial–mesenchymal transition (EMT); karyotyping; mesenchymal–epithelial transition (MET); metabolism; proteomics; RNA-sequencing; seahorse extracellular flux analyser; whole exome sequencing copy number variations (CNV); epithelial–mesenchymal transition (EMT); karyotyping; mesenchymal–epithelial transition (MET); metabolism; proteomics; RNA-sequencing; seahorse extracellular flux analyser; whole exome sequencing
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MDPI and ACS Style

Bhatia, S.; Monkman, J.; Blick, T.; Duijf, P.H.; Nagaraj, S.H.; Thompson, E.W. Multi-Omics Characterization of the Spontaneous Mesenchymal–Epithelial Transition in the PMC42 Breast Cancer Cell Lines. J. Clin. Med. 2019, 8, 1253.

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