Development of an Arteriolar Niche and Self-renewal of Breast Cancer Stem Cells by Lysophosphatidic Acid/protein Kinase D Signaling

Overview

Journal Commun Biol

Specialty Biology

Date 2021 Jun 25

PMID 34168243

Citations 11

Authors

Yinan Jiang

Yichen Guo

Jinjin Hao

Rachael Guenter

Justin Lathia

Adam W Beck

Reagan Hattaway

Douglas Hurst

Qiming Jane Wang

Yehe Liu

Qi Cao

Helen Krontiras

Herbert Chen

Roy Silverstein

Bin Ren

Affiliations

Soon will be listed here.

Abstract

Breast cancer stem cells (BCSCs) are essential for cancer growth, metastasis and recurrence. The regulatory mechanisms of BCSC interactions with the vascular niche within the tumor microenvironment (TME) and their self-renewal are currently under extensive investigation. We have demonstrated the existence of an arteriolar niche in the TME of human BC tissues. Intriguingly, BCSCs tend to be enriched within the arteriolar niche in human estrogen receptor positive (ER) BC and bi-directionally interact with arteriolar endothelial cells (ECs). Mechanistically, this interaction is driven by the lysophosphatidic acid (LPA)/protein kinase D (PKD-1) signaling pathway, which promotes both arteriolar differentiation of ECs and self-renewal of CSCs likely via differential regulation of CD36 transcription. This study indicates that CSCs may enjoy blood perfusion to maintain their stemness features. Targeting the LPA/PKD-1 -CD36 signaling pathway may have therapeutic potential to curb tumor progression by disrupting the arteriolar niche and effectively eliminating CSCs.

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