S1PR1 regulates the switch of two angiogenic modes by VE-cadherin phosphorylation in breast cancer

Cell Death & Disease
Shuang LiuBaocun Sun

Abstract

Angiogenesis in solid tumors is divided into two modes: endothelium-dependent vessel (EDV) and vasculogenic mimicry (VM). Sphingosine-1-phosphate receptor 1 (S1PR1) plays a vital role on EDV in a variety of human tumors. However, the relationship between S1PR1 and VM is not clear. The aim of this study is to investigate S1PR1 on the regulation of EDV and mimicry formation in breast cancer. Here we show that S1PR1 phosphorylates the complex of VE-cadherin to regulate the switch of EDV and mimicry formation. Suppression of S1PR1 impairs EDV, but contributes to the generation of VM, invasion, and metastasis in vivo and vitro. By inhibiting RhoA activation, the S1PR1/VE-cadherin signaling is blocked. S1PR1 controls VE-cadherin expression and EDV via RhoA activation. Moreover, the low expression of S1PR1 correlates with VM and poor prognosis in breast cancer patient. The results show that S1PR1 regulated RhoA activation to accelerate VE-cadherin phosphorylation (Y731), leading to increased EDV and reduced VM in breast cancer. S1PR1 may provide a new thinking direction for antiangiogenic therapy for patients with breast cancer.

References

Jun 21, 2001·Proceedings of the National Academy of Sciences of the United States of America·M J HendrixR E Seftor
May 16, 2002·The Journal of Biological Chemistry·Sarah Spiegel, Sheldon Milstien
Apr 13, 2004·Molecular Biology of the Cell·Celeste M NelsonChristopher S Chen
Nov 4, 2005·Cancer Research·Angela R HessMary J C Hendrix
Dec 27, 2005·Expert Review of Anticancer Therapy·Naohiro FujimotoTetsuro Matsumoto
Apr 9, 2010·Brain : a Journal of Neurology·Soufiane El HallaniMarc Sanson
Oct 27, 2011·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Min SuYuquan Zhang
Jan 24, 2012·Developmental Cell·Xiao Lei ChenDavid D Schlaepfer
Sep 3, 2013·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Zhifei CaoQuansheng Zhou
Jan 20, 2015·Journal of Cellular and Molecular Medicine·Lili QiaoYuan Tian
Apr 2, 2015·The Journal of Clinical Investigation·Richard L Proia, Timothy Hla
Jul 3, 2015·Journal of Cell Science·Luke H HoeppnerDebabrata Mukhopadhyay
Oct 21, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Changhwan YoonSam S Yoon
Nov 26, 2015·Trends in Immunology·Audrey BaeyensSusan R Schwab
Mar 23, 2017·Molecular Cancer·Daniel Delgado-BellidoF Javier Oliver
Jun 18, 2017·Critical Reviews in Biochemistry and Molecular Biology·Timothy RohrbachSarah Spiegel
Feb 13, 2018·Biochemical and Biophysical Research Communications·Takahiro TominoTakehito Uruno
Mar 10, 2018·Nature Reviews. Cancer·Tom DonnemFrancesco Pezzella
Aug 8, 2018·Theranostics·Manendra Babu LankadasariKuzhuvelil B Harikumar
Sep 27, 2018·Frontiers in Oncology·Diana Klein

❮ Previous
Next ❯

Citations

Nov 23, 2019·Cell Death & Disease·Hai-Ping CaiZhong-Ping Chen
Dec 7, 2019·Cancer Cell International·Peng WangXun Qi
Sep 12, 2019·Frontiers in Oncology·Mónica Fernández-CortésF Javier Oliver
Jan 28, 2021·Cancers·Monica MarzagalliPatrizia Limonta
Aug 8, 2021·Cells·Gabriela Morales-GuadarramaLorenza Díaz

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
electrophoresis
fluorescence microscopy
Assay
ELISAs
ELISA
xenograft
GTPase

Software Mentioned

Image
SPSS
- Pro Plus

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.