Year: 2019
Type: dissertation
Abstract: Cancer metabolism has been proposed to adapt the metabolic network from its tissue-of-origin. However, breast cancer is not a disease of a singular origin. There are multiple epithelial subpopulations that serve as the culprit cell-of-origin, giving rise to distinct breast cancer subtypes. Knowledge surrounding the metabolic identities of normal mammary epithelial cells (MEC) is limited. Proteomic profiling of primary FACS-purified human MECs revealed that each subpopulation possesses distinct metabolic networks. Luminal progenitors were enriched for electron transport chain subunits, had an enhanced capacity to undergo oxidative phosphorylation and were vulnerable to Complex I inhibition. Basal cells were more glycolytic, but their progenitor capacity was still dependent on mitochondrial activity. Targeting these pathways with inhibitors exposed lineage-restricted metabolic vulnerabilities. Furthermore, breast cancer subtypes demonstrated significant activity for the metabolic cluster of their cell-of-origin. My work demonstrates that normal MEC have lineage-restricted metabolic identities, which can partly explain the metabolic heterogeneity observed in breast cancer.
Source: TSpace (University of Toronto)
Author: Mathepan Mahendralingam
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3156651885