Endothelial Specific YY1 Deletion Restricts Tumor Angiogenesis and Tumor Growth

Overview

Journal Sci Rep

Specialty Science

Date 2020 Nov 25

PMID 33235311

Citations 7

Authors

Huan Liu

Yikai Qiu

Xiuying Pei

Ramamurthy Chitteti

Rebbeca Steiner

Shuya Zhang

Zheng Gen Jin

Affiliations

Soon will be listed here.

Abstract

Angiogenesis is a physiological process for the formation of new blood vessels from the pre-existing vessels and it has a vital role in the survival and growth of neoplasms. During tumor angiogenesis, the activation of the gene transcriptions in vascular endothelial cells (ECs) plays an essential role in the promotion of EC proliferation, migration, and vascular network development. However, the molecular mechanisms underlying transcriptional regulation of EC and tumor angiogenesis remains to be fully elucidated. Here we report that the transcription factor Yin Yang 1 (YY1) in ECs is critically involved in tumor angiogenesis. First, we utilized a tamoxifen-inducible EC-specific YY1 deficient mouse model and showed that YY1 deletion in ECs inhibited the tumor growth and tumor angiogenesis. Using the in vivo matrigel plug assay, we then found that EC-specific YY1 ablation inhibited growth factor-induced angiogenesis. Furthermore, vascular endothelial growth factor (VEGF)-induced EC migration was diminished in YY1-depleted human umbilical vein endothelial cells (HUVECs). Finally, a rescue experiment revealed that YY1-regulated BMP6 expression in ECs was involved in EC migration. Collectively, our results demonstrate that endothelial YY1 has a crucial role in tumor angiogenesis and suggest that targeting endothelial YY1 could be a potential therapeutic strategy for cancer treatment.

Citing Articles

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Tachibana T, Oyama T, Yoshii Y, Hihara F, Igarashi C, Shinada M Int J Mol Sci. 2023; 24(24).

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Dissecting the roles and clinical potential of YY1 in the tumor microenvironment.

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