Literature DB >> 23712846

Lgr4 regulates mammary gland development and stem cell activity through the pluripotency transcription factor Sox2.

Ying Wang1, Jie Dong, Dali Li, Li Lai, Stefan Siwko, Yi Li, Mingyao Liu.   

Abstract

The key signaling networks regulating mammary stem cells are poorly defined. The leucine-rich repeat containing G protein-coupled receptor (Lgr) family has been implicated in intestinal, gastric, and epidermal stem cell functions. We investigated whether Lgr4 functions in mammary gland development and mammary stem cells. We found that Lgr4(-/-) mice had delayed ductal development, fewer terminal end buds, and decreased side-branching. Crucially, the mammary stem cell repopulation capacity was severely impaired. Mammospheres from Lgr4(-/-) mice showed decreased Wnt signaling. Wnt3a treatment prevented the adverse effects of Lgr4 loss on organoid formation. Chromatin immunoprecipitation analysis indicated that Sox2 expression was controlled by the Lgr4/Wnt/β-catenin/Lef1 pathway. Importantly, Sox2 overexpression restored the in vivo mammary regeneration potential of Lgr4(-/-) mammary stem cells. Therefore, Lgr4 activates Sox2 to regulate mammary development and stem cell functions via Wnt/β-catenin/Lef1. © AlphaMed Press.

Entities:  

Keywords:  Gpr48; Lgr4; Mammary stem cell; Sox2; Wnt signaling

Mesh：

Substances：

Year:  2013        PMID： 23712846      PMCID： PMC3934111          DOI： 10.1002/stem.1438

Source DB:  PubMed          Journal:  Stem Cells        ISSN： 1066-5099            Impact factor:   6.277


  54 in total

1.  In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells.

Authors:  Gabriela Dontu; Wissam M Abdallah; Jessica M Foley; Kyle W Jackson; Michael F Clarke; Mari J Kawamura; Max S Wicha
Journal:  Genes Dev       Date:  2003-05-15       Impact factor: 11.361

2.  Notch signaling regulates mammary stem cell function and luminal cell-fate commitment.

Authors:  Toula Bouras; Bhupinder Pal; François Vaillant; Gwyndolen Harburg; Marie-Liesse Asselin-Labat; Samantha R Oakes; Geoffrey J Lindeman; Jane E Visvader
Journal:  Cell Stem Cell       Date:  2008-10-09       Impact factor: 24.633

3.  Lgr5 marks cycling, yet long-lived, hair follicle stem cells.

Authors:  Viljar Jaks; Nick Barker; Maria Kasper; Johan H van Es; Hugo J Snippert; Hans Clevers; Rune Toftgård
Journal:  Nat Genet       Date:  2008-10-12       Impact factor: 38.330

4.  Collective epithelial migration and cell rearrangements drive mammary branching morphogenesis.

Authors:  Andrew J Ewald; Audrey Brenot; Myhanh Duong; Bianca S Chan; Zena Werb
Journal:  Dev Cell       Date:  2008-04       Impact factor: 12.270

5.  LGR4 regulates the postnatal development and integrity of male reproductive tracts in mice.

Authors:  Takayuki Hoshii; Toru Takeo; Naomi Nakagata; Motohiro Takeya; Kimi Araki; Ken-ichi Yamamura
Journal:  Biol Reprod       Date:  2006-11-01       Impact factor: 4.285

6.  Inactivation of G-protein-coupled receptor 48 (Gpr48/Lgr4) impairs definitive erythropoiesis at midgestation through down-regulation of the ATF4 signaling pathway.

Authors:  Huiping Song; Jian Luo; Weijia Luo; Jinsheng Weng; Zhiqiang Wang; Baoxing Li; Dali Li; Mingyao Liu
Journal:  J Biol Chem       Date:  2008-10-27       Impact factor: 5.157

7.  Deletion of G protein-coupled receptor 48 leads to ocular anterior segment dysgenesis (ASD) through down-regulation of Pitx2.

Authors:  Jinsheng Weng; Jian Luo; Xuhong Cheng; Chang Jin; Xiangtian Zhou; Jia Qu; Lili Tu; Di Ai; Dali Li; Jun Wang; James F Martin; Brad A Amendt; Mingyao Liu
Journal:  Proc Natl Acad Sci U S A       Date:  2008-04-18       Impact factor: 11.205

8.  GPR48 regulates epithelial cell proliferation and migration by activating EGFR during eyelid development.

Authors:  Chang Jin; Furong Yin; Mimi Lin; Hongxia Li; Zhenlian Wang; Jinsheng Weng; Mingyao Liu; Xiang Da Dong; Jia Qu; LiLi Tu
Journal:  Invest Ophthalmol Vis Sci       Date:  2008-05-16       Impact factor: 4.799

9.  Impaired hair placode formation with reduced expression of hair follicle-related genes in mice lacking Lgr4.

Authors:  Yasuaki Mohri; Shigeki Kato; Akihiro Umezawa; Ryuhei Okuyama; Katsuhiko Nishimori
Journal:  Dev Dyn       Date:  2008-08       Impact factor: 3.780

10.  Identification of stem cells in small intestine and colon by marker gene Lgr5.

Authors:  Nick Barker; Johan H van Es; Jeroen Kuipers; Pekka Kujala; Maaike van den Born; Miranda Cozijnsen; Andrea Haegebarth; Jeroen Korving; Harry Begthel; Peter J Peters; Hans Clevers
Journal:  Nature       Date:  2007-10-14       Impact factor: 49.962
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  47 in total

Review 1.  Two Sides of the Same Coin: The Role of Developmental pathways and pluripotency factors in normal mammary stem cells and breast cancer metastasis.

Authors:  M U J Oliphant; Deguang Kong; Hengbo Zhou; M T Lewis; H L Ford
Journal:  J Mammary Gland Biol Neoplasia       Date:  2020-04-22       Impact factor: 2.673

2.  Lgr4 protein deficiency induces ataxia-like phenotype in mice and impairs long term depression at cerebellar parallel fiber-Purkinje cell synapses.

Authors:  Xin Guan; Yanhong Duan; Qingwen Zeng; Hongjie Pan; Yu Qian; Dali Li; Xiaohua Cao; Mingyao Liu
Journal:  J Biol Chem       Date:  2014-07-25       Impact factor: 5.157

3.  RSPO-LGR4 functions via IQGAP1 to potentiate Wnt signaling.

Authors:  Kendra S Carmon; Xing Gong; Jing Yi; Anthony Thomas; Qingyun Liu
Journal:  Proc Natl Acad Sci U S A       Date:  2014-03-17       Impact factor: 11.205

4.  Intraductal Injection of Lentivirus Vectors for Stably Introducing Genes into Rat Mammary Epithelial Cells in Vivo.

Authors:  Wen Bu; Yi Li
Journal:  J Mammary Gland Biol Neoplasia       Date:  2020-11-09       Impact factor: 2.673

5.  Leucine-rich repeat-containing G protein-coupled receptor 4 facilitates vesicular stomatitis virus infection by binding vesicular stomatitis virus glycoprotein.

Authors:  Na Zhang; Hongjun Huang; Binghe Tan; Yinglei Wei; Qingqing Xiong; Yan Yan; Lili Hou; Nannan Wu; Stefan Siwko; Andrea Cimarelli; Jianrong Xu; Honghui Han; Min Qian; Mingyao Liu; Bing Du
Journal:  J Biol Chem       Date:  2017-08-23       Impact factor: 5.157

Review 6.  Unraveling the journey of cancer stem cells from origin to metastasis.

Authors:  Rama Krishna Nimmakayala; Surinder K Batra; Moorthy P Ponnusamy
Journal:  Biochim Biophys Acta Rev Cancer       Date:  2018-11-09       Impact factor: 10.680

7.  The depalmitoylase APT1 directs the asymmetric partitioning of Notch and Wnt signaling during cell division.

Authors:  Ewa Stypulkowski; Irfan A Asangani; Eric S Witze
Journal:  Sci Signal       Date:  2018-01-02       Impact factor: 8.192

Review 8.  Epithelial-mesenchymal transition transcription factors and miRNAs: "Plastic surgeons" of breast cancer.

Authors:  Caroline Moyret-Lalle; Emmanuelle Ruiz; Alain Puisieux
Journal:  World J Clin Oncol       Date:  2014-08-10

Review 9.  Circular RNAs and their participation in stemness of cancer.

Authors:  Francisco Alejandro Lagunas-Rangel
Journal:  Med Oncol       Date:  2020-04-07       Impact factor: 3.064

10.  LGR4 is a receptor for RANKL and negatively regulates osteoclast differentiation and bone resorption.

Authors:  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; Mingyao Liu
Journal:  Nat Med       Date:  2016-04-11       Impact factor: 53.440
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