BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt–β-catenin signaling

He, Xi; Zhang, Jiwang; Tong, Wei; Tawfik, Ossama; Ross, Jason T.; Scoville, David; Tian, Qiang; Zeng, Xin; Wiedemann, Leanne M.; Mishina, Yuji; Li, Linheng

doi:10.1038/ng1430

Cited by 962 publications

(966 citation statements)

References 31 publications

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“…However, Bmp4 expression does become restricted to mesenchymal cells around the SMGs at late stages in their development and this expression persists into adulthood. Here, by analogy with its presumed role in the intestinal crypts (He et al, 2004), it may function to regulate SMG homeostasis. Noggin lacZ , Patched lacz , and Fgf8 LacZ , which are highly expressed in specific cells of the developing hair follicle and tooth bud, were undetectable in or around the SMGs throughout the P2 to P14 period when morphogenesis is occurring (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Intercellular growth factor signaling and the development of mouse tracheal submucosal glands

Rawlins

Hogan

2005

Developmental Dynamics

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To provide a genetic framework for investigating changes in airway submucosal gland function in human respiratory disease, we have investigated their counterparts in normal and mutant mice. We describe their morphogenesis in relation to the expression of genes encoding conserved intercellular signaling pathways. Submucosal glands are severely reduced in number and size in mice heterozygous for Fgf10. Glands are completely absent in mice lacking Ectodysplasin (Eda) and Edaradd (Eda receptor adaptor protein), members of the tumor necrosis (TNF) superfamily of signaling factors. Furthermore, components of the Eda and closely related pathways are transcribed throughout the respiratory system in the adult mouse. Finally, the temporal and spatial pattern of Bmp4 expression suggests that it may control submucosal gland development and homeostasis. Taken together, our observations have important implications for the better understanding of the submucosal gland remodeling that occurs in human respiratory disease.

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Section: Discussionmentioning

confidence: 99%

Intercellular growth factor signaling and the development of mouse tracheal submucosal glands

Rawlins

Hogan

2005

Developmental Dynamics

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“…Epigenetic silencing of tumor suppressor genes by promoter hypermethylation is commonly observed in human cancers 16, 17. DNA methylation may serve as a marker for the differential diagnosis of cancer and as a means of assessing the prognosis of cancer patients 18, 19, 20, 21. Aberrant DNA methylation is a common epigenetic event leading to the inactivation of tumor suppressor genes in ovarian cancer 22, 23.…”

mentioning

confidence: 99%

Distinct methylation profile of mucinous ovarian carcinoma reveals susceptibility to proteasome inhibitors

Liew

Huang

Weng

et al. 2018

Intl Journal of Cancer

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Mucinous type of epithelial ovarian cancer (MuOC) is a unique subtype with a poor survival outcome in recurrent and advanced stages. The role of type‐specific epigenomics and its clinical significance remains uncertain. We analyzed the methylomic profiles of 6 benign mucinous adenomas, 24 MuOCs, 103 serous type of epithelial ovarian cancers (SeOCs) and 337 nonepithelial ovarian cancers. MuOC and SeOC exhibited distinct DNA methylation profiles comprising 101 genes, 81 of which exhibited low methylation in MuOC and were associated with the response to glucocorticoid, ATP hydrolysis‐coupled proton transport, proteolysis involved in the cellular protein catabolic process and ion transmembrane transport. Hierarchical clustering analysis showed that the profiles of MuOC were similar to colorectal adenocarcinoma and stomach adenocarcinoma. Genetic interaction network analysis of differentially methylated genes in MuOC showed a dominant network module is the proteasome subunit beta (PSMB) family. Combined functional module and methylation analysis identified PSMB8 as a candidate marker for MuOC. Immunohistochemical staining of PSMB8 used to validate in 94 samples of ovarian tumors (mucinous adenoma, MuOC or SeOC) and 62 samples of gastrointestinal cancer. PSMB8 was commonly expressed in MuOC and gastrointestinal cancer samples, predominantly as strong cytoplasmic and occasionally weak nuclei staining, but was not expressed in SeOC samples. Carfilzomib, a second‐generation proteasome inhibitor, suppressed MuOC cell growth in vitro. This study unveiled a mucinous‐type‐specific methylation profile and suggests the potential use of a proteasome inhibitor to treat MuOC.

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“…In mesenchymal stem cells, the BMP signal induces osteoblastic differentiation through Bmpr1b but inhibits osteoblastic differentiation through Bmpr1a 45. BMP signaling inhibits stem cell activation and expansion in intestinal stem cells 46. In hematopoietic stem cells, BMP signaling through Bmpr1a restricts stem cell number by controlling the niche size 47…”

Section: Liver Stem Cells and Tgf‐β: Evidence From Mouse Knockout LImentioning

confidence: 99%

Transforming growth factor‐β in liver cancer stem cells and regeneration

Rao

Zaidi

Banerjee

et al. 2017

Hepatology Communications

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Cancer stem cells have established mechanisms that contribute to tumor heterogeneity as well as resistance to therapy. Over 40% of hepatocellular carcinomas (HCCs) are considered to be clonal and arise from a stem‐like/cancer stem cell. Moreover, HCC is the second leading cause of cancer death worldwide, and an improved understanding of cancer stem cells and targeting these in this cancer are urgently needed. Multiple studies have revealed etiological patterns and multiple genes/pathways signifying initiation and progression of HCC; however, unlike the transforming growth factor β (TGF‐β) pathway, loss of p53 and/or activation of β‐catenin do not spontaneously drive HCC in animal models. Despite many advances in cancer genetics that include identifying the dominant role of TGF‐β signaling in gastrointestinal cancers, we have not reached an integrated view of genetic mutations, copy number changes, driver pathways, and animal models that support effective targeted therapies for these common and lethal cancers. Moreover, pathways involved in stem cell transformation into gastrointestinal cancers remain largely undefined. Identifying the key mechanisms and developing models that reflect the human disease can lead to effective new treatment strategies. In this review, we dissect the evidence obtained from mouse and human liver regeneration, and mouse genetics, to provide insight into the role of TGF‐β in regulating the cancer stem cell niche. (Hepatology Communications 2017;1:477–493)

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BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt–β-catenin signaling

Cited by 962 publications

References 31 publications

Intercellular growth factor signaling and the development of mouse tracheal submucosal glands

Intercellular growth factor signaling and the development of mouse tracheal submucosal glands

Distinct methylation profile of mucinous ovarian carcinoma reveals susceptibility to proteasome inhibitors

Transforming growth factor‐β in liver cancer stem cells and regeneration

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