ASPSCR1::TFE3 orchestrates the angiogenic program of alveolar soft part sarcoma

Miwa Tanaka (), Surachada Chuaychob, Mizuki Homme, Yukari Yamazaki, Ruyin Lyu, Kyoko Yamashita, Keisuke Ae, Seiichi Matsumoto, Kohei Kumegawa, Reo Maruyama, Wei Qu, Yohei Miyagi, Ryuji Yokokawa and Takuro Nakamura ()
Additional contact information
Miwa Tanaka: Division of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research
Surachada Chuaychob: Kyoto University
Mizuki Homme: Division of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research
Yukari Yamazaki: Division of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research
Ruyin Lyu: Kyoto University
Kyoko Yamashita: Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research
Keisuke Ae: Cancer Institute Hospital, Japanese Foundation for Cancer Research
Seiichi Matsumoto: Cancer Institute Hospital, Japanese Foundation for Cancer Research
Kohei Kumegawa: Project for Cancer Epigenomics, The Cancer Institute, Japanese Foundation for Cancer Research
Reo Maruyama: Project for Cancer Epigenomics, The Cancer Institute, Japanese Foundation for Cancer Research
Wei Qu: The University of Tokyo
Yohei Miyagi: Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute
Ryuji Yokokawa: Kyoto University
Takuro Nakamura: Division of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Alveolar soft part sarcoma (ASPS) is a soft part malignancy affecting adolescents and young adults. ASPS is characterized by a highly integrated vascular network, and its high metastatic potential indicates the importance of ASPS’s prominent angiogenic activity. Here, we find that the expression of ASPSCR1::TFE3, the fusion transcription factor causatively associated with ASPS, is dispensable for in vitro tumor maintenance; however, it is required for in vivo tumor development via angiogenesis. ASPSCR1::TFE3 is frequently associated with super-enhancers (SEs) upon its DNA binding, and the loss of its expression induces SE-distribution dynamic modification related to genes belonging to the angiogenesis pathway. Using epigenomic CRISPR/dCas9 screening, we identify Pdgfb, Rab27a, Sytl2, and Vwf as critical targets associated with reduced enhancer activities due to the ASPSCR1::TFE3 loss. Upregulation of Rab27a and Sytl2 promotes angiogenic factor-trafficking to facilitate ASPS vascular network construction. ASPSCR1::TFE3 thus orchestrates higher ordered angiogenesis via modulating the SE activity.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-37049-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37049-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-37049-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().