Purpose: Pharmacology-based target identification has become a novel stratey leading to the discovery of novel pathological biomarkers. Ellagic acid (EA), a dietary polyphenol compound, exhibits potent anticancer activities, whereas the underlying mechanisms remain unclear. This study sought to determine the role and regulation of ACTN4 expression in human breast cancer metastasis and EA-based therapy.

Experimental Design: The anti-metastasis ability of EA was validated by MMTV-PyMT mice and in vitro cell models. Drug affiity responsive target stability (DARTS) was utilized to identify ACTN4 as the direct target of EA in breast breast cancer stem cells (CSCs). The metastatic regulated mechanisms of ACTN4 were assessed by CSC-related assays including mammosphere formation, tumorigenic ability, reattachment differentiation and signaling pathway analysis. The clinical significance of ACTN4 was based on human tissue microarray analysis and TCGA database exploration.

Results: EA inhibited breast cancer growth and metastasis via directly targeting ACTN4 in vitro and in vivo, accompanied with limited CSCs population. ACTN4 knockdown resulted in blockage of malignant cell proliferation, colony formation and ameliorated metastasis potency. ACTN4 positive CSCs exhibited higher ESA+ proportion, increased mammosphere-formation ability, as well as enhanced in vivo tumorigenesis ability. Increased ACTN4 expression was directly associated with later cancer stage, increased incidence of metastasis, and poor overall survival period.

Conclusions: ACTN4 plays an important role in breast CSCs-related metastasis and is a novel therapeutic target of EA treatment.

Note: This abstract was not presented at the meeting.

Citation Format: Neng Wang, Zhiyu Wang, Xiaoming Xie. Actn4, a novel therapeutic target of dietary ellagic acid, promotes breast cancer metastasis via mediating cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1912. doi:10.1158/1538-7445.AM2017-1912