RT Journal Article
SR Electronic
T1 Mammary epithelial cells have lineage-restricted metabolic identities
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 798173
DO 10.1101/798173
A1 Mathepan Mahendralingam
A1 Kazeera Aliar
A1 Alison Elisabeth Casey
A1 Davide Pellacani
A1 Hyeyeon Kim
A1 Vladimir Ignatchenko
A1 Mar Garcia Valero
A1 Luis Palomero
A1 Ankit Sinha
A1 Vid Stambolic
A1 Mina Alam
A1 Aaron Schimmer
A1 Hal Berman
A1 Miquel Angel Pujana
A1 Connie Eaves
A1 Thomas Kislinger
A1 Rama Khokha
YR 2019
UL http://biorxiv.org/content/early/2019/10/08/798173.abstract
AB Cancer metabolism adapts the metabolic network of its tissue-of-origin. However, breast cancer is not a disease of a singular origin. Multiple epithelial populations serve as the culprit cell-of-origin for specific breast cancer subtypes, yet knowledge surrounding the metabolic network of normal mammary epithelial cells is limited. Here, we show that mammary populations have cell type-specific metabolic programs. Primary human breast cell proteomes of basal, luminal progenitor, and mature luminal populations revealed their unique enrichment of metabolic proteins. Luminal progenitors had higher abundance of electron transport chain subunits and capacity for oxidative phosphorylation, whereas basal cells were more glycolytic. Targeting oxidative phosphorylation and glycolysis with inhibitors exposed distinct metabolic vulnerabilities of the mammary lineages. Computational analysis indicated that breast cancer subtypes retain metabolic features of their putative cell-of-origin. Lineage-restricted metabolic identities of normal mammary cells partly explain breast cancer metabolic heterogeneity and rationalize targeting subtype-specific metabolic vulnerabilities to advance breast cancer therapy.