Epigenetic Changes in Fibroblasts Drive Cancer Metabolism and Differentiation

Overview

Journal Endocr Relat Cancer

Specialties Endocrinology
Oncology

Date 2019 Oct 19

PMID 31627186

Citations 25

Authors

Rajeev Mishra

Subhash Haldar

Surabhi Suchanti

Neil A Bhowmick

Affiliations

Soon will be listed here.

Abstract

Genomic changes that drive cancer initiation and progression contribute to the co-evolution of the adjacent stroma. The nature of the stromal reprogramming involves differential DNA methylation patterns and levels that change in response to the tumor and systemic therapeutic intervention. Epigenetic reprogramming in carcinoma-associated fibroblasts are robust biomarkers for cancer progression and have a transcriptional impact that support cancer epithelial progression in a paracrine manner. For prostate cancer, promoter hypermethylation and silencing of the RasGAP, RASAL3 that resulted in the activation of Ras signaling in carcinoma-associated fibroblasts. Stromal Ras activity initiated a process of macropinocytosis that provided prostate cancer epithelia with abundant glutamine for metabolic conversion to fuel its proliferation and a signal to transdifferentiate into a neuroendocrine phenotype. This epigenetic oncogenic metabolic/signaling axis seemed to be further potentiated by androgen receptor signaling antagonists and contributed to therapeutic resistance. Intervention of stromal signaling may complement conventional therapies targeting the cancer cell.

Citing Articles

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TGF-β controls stromal telomere length through epigenetic modifications.

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