Editorial Material
Biochemistry & Molecular Biology
Ermanno Malagola, Yoku Hayakawa, Timothy C. Wang
Summary: Recent research has identified distinct roles for Lgr4 and Lgr5 in directing gland reconstitution following H. pylori infection, shedding new light on the complexities of Rspo signaling during gastric regeneration and raising questions about antral stem cell hierarchy.
Article
Medicine, Research & Experimental
Cecily Lucas, Kay-Sara Sauter, Michael Steigert, Delphine Mallet, James Wilmouth, Julie Olabe, Ingrid Plotton, Yves Morel, Daniel Aeberli, Franca Wagner, Hans Clevers, Amit V. Pandey, Pierre Val, Florence Roucher-Boulez, Christa E. Flueck
Summary: This article describes a highly consanguineous family with multiple perinatal deaths and infants presenting at birth with failure to thrive, severe salt-wasting crises associated with isolated hypoaldosteronism, nail anomalies, short stature, and deafness. Whole exome sequencing revealed a homozygous splice variant in the R-SPONDIN receptor LGR4 gene (c.618-1G>C) regulating WNT signaling. The impact of LGR4 inactivation was analyzed by adrenal cortex-specific ablation of Lgr4, which resulted in abnormal zG differentiation and endocrine function.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Hematology
Antonina Kurtova, Melanie Heinlein, Simon Haas, Lars Velten, Gerrit J. P. Dijkgraaf, Elaine E. Storm, Noelyn M. Kljavin, Soufiane Boumahdi, Patricia Himmels, Aurelie Herault, Andrew Mancini, Hartmut Koeppen, Monique Dail, Qingxiang Yan, Jianhuan Zhang, Ute Koch, Freddy Radtke, Zora Modrusan, Ciara Metcalfe, Robert Piskol, Frederic J. de Sauvage
Summary: The self-renewal and differentiation of stem and progenitor cells are regulated by systemic and local cues. RSPO3 is important for Wnt signaling and is usually expressed in the stem cell niche to regulate stem cell expansion and differentiation. Disrupting the niche-restricted expression of RSPO3 can affect tissue organization and lead to disorders and cancers.
Article
Biochemistry & Molecular Biology
Jonas Wizenty, Stefanie Muellerke, Marina Kolesnichenko, Julian Heuberger, Manqiang Lin, Anne-Sophie Fischer, Hans-Joachim Mollenkopf, Hilmar Berger, Frank Tacke, Michael Sigal
Summary: Helicobacter pylori is a pathogen that causes chronic gastritis by colonizing the stomach. This study found that Rspo3 signaling through Lgr4 regulates the proliferation of stem cells and induces NF-kappa B activity in proliferating stem cells. The invasion of H. pylori leads to Lgr4-driven NF-kappa B activation, resulting in expansion of the gland base module and chemokine expression in stem cells, leading to gland hyperplasia and neutrophil recruitment.
Article
Oncology
Fei Yue, Weiyu Jiang, Amy T. Ku, Adelaide I. J. Young, Weijie Zhang, Eric P. Souto, Yankun Gao, Zihan Yu, Yi Wang, Chad J. Creighton, Chandandeep Nagi, Tao Wang, Susan G. Hilsenbeck, Xin-Hua Feng, Shixia Huang, Cristian Coarfa, Xiang H-F Zhang, Qingyun Liu, Xia Lin, Yi Li
Summary: The mechanism by which LGR4 promotes cancer metastasis is independent of the Wnt signaling pathway and involves interaction with EGFR to block its degradation, leading to increased migration and invasion of cancer cells.
Article
Multidisciplinary Sciences
Yukimatsu Toh, Ling Wu, Soohyun Park, Allison Wang, Jianghua Tu, Wangsheng Yu, Mingxin Zuo, Kendra S. Carmon, Qingyun J. Liu
Summary: LGR4 and LGR5 are homologous receptors that enhance Wnt/β-catenin signaling in response to RSPO ligands. While the RSPO and LGR4 complex binds to and inhibits E3 ligases RNF43 and ZNRF3, the RSPO and LGR5 complex does not interact with the E3 ligases. The underlying structural basis for this difference is still unknown.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Medicinal
Jie Cui, Yukimatsu Toh, Soohyun Park, Wangsheng Yu, Jianghua Tu, Ling Wu, Li Li, Joan Jacob, Sheng Pan, Kendra S. Carmon, Qingyun J. Liu
Summary: LGR4-6 are related receptors commonly upregulated in gastrointestinal cancers, with LGR5 being enriched in cancer stem cells. Targeting all three LGRs simultaneously is proposed for a more effective anti-tumor approach. A drug conjugate comprising an RSPO4 mutant and IgG1-Fc showed potent cytotoxic effects on cancer cells expressing any LGR, suppressing tumor growth without adverse effects.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Eline J. ter Steege, Elvira R. M. Bakker
Summary: RSPO proteins play a crucial role in activating the Wnt/beta-catenin signaling pathway in stem cells and progenitor cells. Deregulation of RSPOs has been implicated in various cancer types, with potential for therapeutic targeting in cancer cases with RSPO overrepresentation.
Article
Oncology
Eline J. ter Steege, Loes W. Doornbos, Peter D. Haughton, Paul J. van Diest, John Hilkens, Patrick W. B. Derksen, Elvira R. M. Bakker
Summary: We have identified RSPO3 as a novel driver of breast cancer, independent of Wnt signaling, and it promotes the proliferation and invasion of breast cancer cells. In contrast to colorectal cancer, Wnt inhibitors are not effective in RSPO3-driven breast cancer, but directly targeting RSPO3 effectively inhibits the growth of breast cancer cells. Our findings suggest that RSPO3 is a valuable therapeutic target in breast cancer.
Article
Biology
Kenichi Nagano, Kei Yamana, Hiroaki Saito, Riku Kiviranta, Ana Clara Pedroni, Dhairya Raval, Christof Niehrs, Francesca Gori, Roland Baron
Summary: Activation of Wnt signaling by Rspo3 deficiency leads to increased bone mass in appendicular skeleton but decreased bone mass in axial skeleton. Rspo3 deficiency impairs the inhibitory effect of Dkk1 on Wnt signaling activation, leading to the activation of Erk signaling and stabilization of beta-catenin, favoring osteoblastogenesis, bone formation, and bone mass.
Article
Biochemistry & Molecular Biology
Rui Sun, Zibo Meng, Hyeyoon Lee, Rienk Offringa, Christof Niehrs
Summary: ROTACs are a promising therapeutic intervention technology that can target cell surface proteins for degradation. By using RSPO and ZNRF3/RNF43 E3 transmembrane ligases, researchers have developed ROTACs to specifically degrade the immune checkpoint protein PD-L1. Experimental results show that ROTACs can reactivate cytotoxic T cells and inhibit tumor cell proliferation more effectively.
CELL CHEMICAL BIOLOGY
(2023)
Article
Agriculture, Multidisciplinary
Jia-yi Zhou, Geng-xiu Zan, Qiu-jie Zhu, Chun-qi Gao, Hui-chao Yan, Xiu-qi Wang
Summary: This study cloned the porcine RSPO1 gene and obtained rpRSPO1 protein, and demonstrated the stimulatory effect of rpRSPO1 on jejunal epithelial cell proliferation using in vitro and in vivo models. It also showed that rpRSPO1 could ameliorate growth retardation and maintain epithelial integrity in mice, and increase ISC activity by activating the Wnt/β-catenin pathway.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Cell Biology
Xue Tan, Lingling Zhang, Tianqi Li, Jianmin Zhan, Kun Qiao, Haili Wu, Shenfei Sun, Meina Huang, Fangxi Zhang, Meixing Zhang, Changwei Li, Runsheng Li, Hongjie Pan
Summary: The WNT signaling pathway plays a crucial role in the development of fallopian tubes in mice, with LGR4 regulating epithelial secretion and affecting tube size and cell number. This regulation is mediated by modulation of the WNT pathway and changes in gene expression profiles of epithelial cells. Additionally, activation of the WNT pathway triggers the expression of steroidogenic genes through the transcription factor NR5A2, facilitating epithelial secretory cell maturation and steroidogenesis for fallopian tube development and function.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Abdulkhaliq Alsaadi, Mara Artibani, Zhiyuan Hu, Nina Wietek, Matteo Morotti, Laura Santana Gonzalez, Moiad Alazzam, Jason Jiang, Beena Abdul, Hooman Soleymani Majd, Levi L. Blazer, Jarret Adams, Francesca Silvestri, Sachdev S. Sidhu, Joan S. Brugge, Ahmed Ashour Ahmed
Summary: The study addresses the limited knowledge about fallopian tube (FT) stem cells and lack of in vitro models for their renewal and differentiation. It identifies the importance of WNT/β-catenin signaling for FT stem cell renewal and the critical role of an endogenous hormone-regulated WNT7A-FZD5 signaling axis in this process.
Article
Biochemistry & Molecular Biology
Yijun Chen, Zhujin Lu, Jiaxin Feng, Zefeng Chen, Zejian Liu, Xiuqi Wang, Huichao Yan, Chunqi Gao
Summary: In this study, it was found that treatment with rRSPO1 can activate hair follicle stem cells in mice and accelerate hair regeneration. rRSPO1 improves hair follicle development and promotes hair growth by activating the Wnt/β-catenin signaling pathway.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2023)
Review
Chemistry, Multidisciplinary
SooHyun Park, You Jung Kang, Sheereen Majd
ADVANCED MATERIALS
(2015)
Article
Biochemistry & Molecular Biology
Georgios Vassilakos, Hanqin Lei, Yun Yang, Jason Puglise, Michael Matheny, Julia Durzynska, Matan Ozery, Katherine Bennett, Ray Spradlin, Heather Bonanno, Soohyun Park, Rexford S. Ahima, Elisabeth R. Barton
Article
Multidisciplinary Sciences
SooHyun Park, Sheereen Majd
Article
Chemistry, Multidisciplinary
SooHyun Park, Guang Yang, Nrutya Madduri, Mohammad Reza Abidian, Sheereen Majd
ADVANCED MATERIALS
(2014)
Article
Endocrinology & Metabolism
Becky K. Brisson, Janelle Spinazzola, SooHyun Park, Elisabeth R. Barton
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2014)
Article
Biochemistry & Molecular Biology
Elisabeth R. Barton, SooHyun Park, Jose K. James, Catherine A. Makarewich, Anastassios Philippou, Davide Eletto, Hanqin Lei, Becky Brisson, Olga Ostrovsky, Zihai Li, Yair Argon
Article
Physiology
SooHyun Park, Becky K. Brisson, Min Liu, Janelle M. Spinazzola, Elisabeth R. Barton
JOURNAL OF APPLIED PHYSIOLOGY
(2014)
Article
Clinical Neurology
Elisabeth R. Barton, Jennifer Pham, Becky K. Brisson, SooHyun Park, Lucas R. Smith, Min Liu, Zuozhen Tian, David W. Hammers, Georgios Vassilakos, H. Lee Sweeney
Article
Multidisciplinary Sciences
Rui Jiang, Steven Vandal, SooHyun Park, Sheereen Majd, Erkan Tuzel, William O. Hancock
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Multidisciplinary Sciences
Jianghua Tu, Soohyun Park, Wangsheng Yu, Sheng Zhang, Ling Wu, Kendra Carmon, Qingyun J. Liu
SCIENTIFIC REPORTS
(2019)
Article
Biochemistry & Molecular Biology
Soohyun Park, Ling Wu, Jianghua Tu, Wangsheng Yu, Yukimatsu Toh, Kendra S. Carmon, Qingyun J. Liu
Proceedings Paper
Biophysics
SooHyun Park, Mohammad R. Abidian, Sheereen Majd
2017 39TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC)
(2017)