Down Syndrome Candidate Region 1 Isoform 1L regulated tumor growth by targeting both angiogenesis and tumor cells.

Autor: Chen C; Center for Vascular Biology Research and Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA; Department of Surgery of Breast and Thyroid, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China., Cui P; Center for Vascular Biology Research and Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA; Pancreatic Disease Institute, Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China., Zhao K; Center for Vascular Biology Research and Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA., Niu G; Center for Vascular Biology Research and Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA; Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China., Hou S; Center for Vascular Biology Research and Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA; Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China., Zhao D; Center for Vascular Biology Research and Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA., Zeng H; Center for Vascular Biology Research and Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. Electronic address: zengzhaonorth@outlook.com.
Jazyk: angličtina
Zdroj: Microvascular research [Microvasc Res] 2022 Mar; Vol. 140, pp. 104305. Date of Electronic Publication: 2021 Dec 24.
DOI: 10.1016/j.mvr.2021.104305
Abstrakt: Angiogenesis is critical for solid tumor growth beyond its minimal size. Previously, we reported that Down Syndrome Candidate Region 1 isoform 1L (DSCR1-1L) was one of the most up-regulated genes in endothelial cells induced by VEGF and histamine, and regulated endothelial cell proliferation, migration and angiogenesis. However, it was not known whether DSCR1-1L played a role in tumor growth. In this study, we found that DSCR1-1L shRNAs significantly inhibited the growth of transplanted melanoma in mice and its associated tumoral angiogenesis. In the gain of function assay, overexpression of DSCR1-1L cDNA in mouse endothelium is sufficient to significantly increase the tumor initiation induced by carcinogen, the growth of xenografted tumor, and the tumor metastasis in our endothelially-expressed DSCR1-1L transgenic mice, in which angiogenesis was induced. It was the first time to find that DSCR1-1L was also expressed in various tumor cells. DSCR1-1L shRNAs inhibited, but overexpression of DSCR1-1L cDNA increased, the tumor cell proliferation and migration. Most recently, we reported that DSCR1-1L modulated angiogenesis by down-regulation of VE-cadherin expression. Here, we found that DSCR1-1L down-regulated the expression of E-cadherin. Hence, DSCR1-1L is an excellent therapeutic target for cancers by regulation of both the endothelial and tumor cells through down-regulating (V)E-cadherin. DSCR1-1L shRNAs have the potential to be developed for clinical application.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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