Drug specific epigenetic reprogramming leads to increased cellular invasion in ERα positive breast cancer via de novo cholesterol biosynthesis.

ABSTRACT: Endocrine therapy resistance remains a critical problem in the treatment of estrogen receptor alpha (ERα) breast cancer. Endocrine therapies target ERα via different modes of action. Drug resistance involves drug specific remodeling of the transcriptional and regulatory landscape. Using epigenomics and transcriptomics, we demonstrate that resistance to aromatase inhibitors (AI) induces phenotypical changes through epigenetic activation of cholesterol biosynthesis (CB) and keratin 80. Epigenetic activation is stable and involves both large topological domains and punctuated activation of single enhancers and super-enhancers. Specialized cancer cells expressing high levels of keratin 80 lead invasion through the extracellular matrix. Strikingly, we demonstrate that anti-cholesterol strateg

ORGANISM(S): Homo sapiens

SUBMITTER: Luca Magnani 

PROVIDER: E-GEOD-60517 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress