GPR116, an adhesion G-protein-coupled receptor, promotes breast cancer metastasis via the Gαq-p63RhoGEF-Rho GTPase pathway.
Xiaolong Tang,Rongrong Jin,Guojun Qu,Xiu Wang,Zhenxi Li,Zengjin Yuan,Chen Zhao,Stefan Siwko,Tieliu Shi,Ping Wang,Jianru Xiao,Mingyao Liu,Jian Luo +12 more
TLDR
Findings show that GPR 116 is crucial for the metastasis of breast cancer and support GPR116 as a potential prognostic marker and drug target against metastatic human breast cancer.Abstract:
Adhesion G-protein-coupled receptors (GPCR), which contain adhesion domains in their extracellular region, have been found to play important roles in cell adhesion, motility, embryonic development, and immune response. Because most adhesion molecules with adhesion domains have vital roles in cancer metastasis, we speculated that adhesion GPCRs are potentially involved in cancer metastasis. In this study, we identified GPR116 as a novel regulator of breast cancer metastasis through expression and functional screening of the adhesion GPCR family. We found that knockdown of GPR116 in highly metastatic (MDA-MB-231) breast cancer cells suppressed cell migration and invasion. Conversely, ectopic GPR116 expression in poorly metastatic (MCF-7 and Hs578T) cells promoted cell invasion. We further showed that knockdown of GPR116 inhibited breast cancer cell metastasis in two mammary tumor metastasis mouse models. Moreover, GPR116 modulated the formation of lamellipodia and actin stress fibers in cells in a RhoA- and Rac1-dependent manner. At a molecular level, GPR116 regulated cell motility and morphology through the Gαq-p63RhoGEF-RhoA/Rac1 pathway. The biologic significance of GPR116 in breast cancer is substantiated in human patient samples, where GPR116 expression is significantly correlated with breast tumor progression, recurrence, and poor prognosis. These findings show that GPR116 is crucial for the metastasis of breast cancer and support GPR116 as a potential prognostic marker and drug target against metastatic human breast cancer.read more
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International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors
Jörg Hamann,Gabriela Aust,Demet Araç,Felix B. Engel,Caroline J. Formstone,Robert Fredriksson,Randy A. Hall,Breanne L. Harty,Christiane Kirchhoff,Barbara Knapp,Arunkumar Krishnan,Ines Liebscher,Hsi-Hsien Lin,David C. Martinelli,Kelly Monk,Miriam C. Peeters,Xianhua Piao,Simone Prömel,Torsten Schöneberg,Thue W. Schwartz,Kathleen Singer,Martin Stacey,Yuri A. Ushkaryov,Mario Vallon,Uwe Wolfrum,Mathew W. Wright,Lei Xu,Tobias Langenhan,Helgi B. Schiöth +28 more
TL;DR: This review covers all major biologic aspects of Adhesion GPCRs, including evolutionary origins, interaction partners, signaling, expression, physiologic functions, and therapeutic potential.
Journal ArticleDOI
LGR4 is a receptor for RANKL and negatively regulates osteoclast differentiation and bone resorption.
Jian Luo,Zhengfeng Yang,Yu Ma,Zhiying Yue,Hongyu Lin,Guojun Qu,Jinping Huang,Wentao Dai,Chenghai Li,Chunbing Zheng,Leqin Xu,Huaqing Chen,Jiqiu Wang,Dali Li,Stefan Siwko,Josef M. Penninger,Guang Ning,Jianru Xiao,Jianru Xiao,Mingyao Liu,Mingyao Liu +20 more
TL;DR: It is reported that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL that negatively regulates osteoclast differentiation and bone resorption.
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Novel insights into G protein and G protein-coupled receptor signaling in cancer
TL;DR: Understanding GPCR involvement in cancer malignancy may help identify novel therapeutic opportunities for cancer prevention and treatment.
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Identification of Key Candidate Genes and Pathways in Colorectal Cancer by Integrated Bioinformatical Analysis.
TL;DR: Using integrated bioinformatical analysis, DEGs candidate genes and pathways in CRC are identified, which could improve the understanding of the cause and underlying molecular events, and these candidate gene and pathways could be therapeutic targets for CRC.
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Astrocytic TYMP and VEGFA drive blood-brain barrier opening in inflammatory central nervous system lesions
Candice Chapouly,Azeb Tadesse Argaw,Sam Horng,Kamilah Castro,Jingya Zhang,Linnea Asp,Hannah Loo,Benjamin M. Laitman,John N. Mariani,Rebecca Straus Farber,Elena Zaslavsky,German Nudelman,Cedric S. Raine,Gareth R. John +13 more
TL;DR: Data identify thymidine phosphorylase (TYMP) as an astrocyte-derived permeability factor, and suggest TYMP and VEGFA together promote blood-brain barrier breakdown.
References
More filters
Journal ArticleDOI
Global cancer statistics
TL;DR: A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination, and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake.
Journal ArticleDOI
Rho GTPases and the Actin Cytoskeleton
TL;DR: Members of the Rho family of small guanosine triphosphatases have emerged as key regulators of the actin cytoskeleton, and through their interaction with multiple target proteins, they ensure coordinated control of other cellular activities such as gene transcription and adhesion.
Journal ArticleDOI
Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia
Catherine D. Nobes,Alan Hall +1 more
TL;DR: It is reported here that cdc42, another member of the rho family, triggers the formation of a third type of actin-based structure found at the cell periphery, filopodia, in addition to stress fibers, and rho controls the assembly of focal adhesion complexes.
Journal ArticleDOI
The small GTP-binding protein rac regulates growth factor-induced membrane ruffling.
TL;DR: It is proposed that rac and rho are essential components of signal transduction pathways linking growth factors to the organization of polymerized actin and that growth factors act through rac to stimulate this rho-dependent response.
Journal ArticleDOI
RHO-GTPases and cancer.
TL;DR: The RAS oncogenes are members of a large family of small GTPases that bind GTP and hydrolyse it to GDP and the switching between these two states regulates a wide range of cellular processes.
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International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors
Jörg Hamann,Gabriela Aust,Demet Araç,Felix B. Engel,Caroline J. Formstone,Robert Fredriksson,Randy A. Hall,Breanne L. Harty,Christiane Kirchhoff,Barbara Knapp,Arunkumar Krishnan,Ines Liebscher,Hsi-Hsien Lin,David C. Martinelli,Kelly Monk,Miriam C. Peeters,Xianhua Piao,Simone Prömel,Torsten Schöneberg,Thue W. Schwartz,Kathleen Singer,Martin Stacey,Yuri A. Ushkaryov,Mario Vallon,Uwe Wolfrum,Mathew W. Wright,Lei Xu,Tobias Langenhan,Helgi B. Schiöth +28 more