N-Sulfation of Heparan Sulfate Regulates Early Branching Events in the Developing Mammary Gland

Bush, Kevin T.; Crawford, Brett E.; Garner, Omai B.; Nigam, Kabir B.; Nigám, Sanjay K.

doi:10.1074/jbc.m112.423327

Cited by 15 publications

(12 citation statements)

References 35 publications

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“…Garner et al showed that lack of HS primary central core, after deletion of Ext1, the enzyme responsible for building up the central core of 1,4-linked uronic acid (D-glucuronic acid or L-iduronic acid) and D-glucosamine, results in highly defective mammary development [20]. It was also shown that N-sulfation is very important for mammary gland development, since N-deacetylase/N-sulfotransferase (NDST) 1 and 2 depletion results in hyperbranching [21], and specific deletion of NDST1 inhibits lobuloalveolar expansion [22]. Additionally, HSPGs expression seems to fluctuate along menstrual cycle [23], an indication that these molecules also have a role in the maintenance of the adult tissue.…”

Section: Heparan Sulfate In Breast Cancermentioning

confidence: 99%

Heparan Sulfate and Heparanase as Modulators of Breast Cancer Progression

Gomes

Stelling

Pavão

2013

BioMed Research International

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Breast cancer is defined as a cancer originating in tissues of the breast, frequently in ducts and lobules. During the last 30 years, studies to understand the biology and to treat breast tumor improved patients' survival rates. These studies have focused on genetic components involved in tumor progression and on tumor microenvironment. Heparan sulfate proteoglycans (HSPGs) are involved in cell signaling, adhesion, extracellular matrix assembly, and growth factors storage. As a central molecule, HSPG regulates cell behavior and tumor progression. HS accompanied by its glycosaminoglycan counterparts regulates tissue homeostasis and cancer development. These molecules present opposite effects according to tumor type or cancer model. Studies in this area may contribute to unveil glycosaminoglycan activities on cell dynamics during breast cancer exploring these polysaccharides as antitumor agents. Heparanase is a potent tumor modulator due to its protumorigenic, proangiogenic, and prometastatic activities. Several lines of evidence indicate that heparanase is upregulated in all human sarcomas and carcinomas. Heparanase seems to be related to several aspects regulating the potential of breast cancer metastasis. Due to its multiple roles, heparanase is seen as a target in cancer treatment. We will describe recent findings on the function of HSPGs and heparanase in breast cancer behavior and progression.

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Section: Heparan Sulfate In Breast Cancermentioning

confidence: 99%

Heparan Sulfate and Heparanase as Modulators of Breast Cancer Progression

Gomes

Stelling

Pavão

2013

BioMed Research International

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“…Despite the critical roles of HS in the development of mammalian organs, especially those generated from branching morphogenesis [ 15 – 20 ], limited studies have unveiled the role of HS in the context of lung development. Mice deficient in N-deacetylase/N-sulfotransferase-1 (NDST1) had disrupted BMP signaling and displayed a lung atelectasis associated with differentiation defects [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Epithelial heparan sulfate regulates Sonic Hedgehog signaling in lung development

Huang

Sun

et al. 2017

PLoS Genet

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The tree-like structure of the mammalian lung is generated from branching morphogenesis, a reiterative process that is precisely regulated by numerous factors. How the cell surface and extra cellular matrix (ECM) molecules regulate this process is still poorly understood. Herein, we show that epithelial deletion of Heparan Sulfate (HS) synthetase Ext1 resulted in expanded branching tips and reduced branching number, associated with several mesenchymal developmental defects. We further demonstrate an expanded Fgf10 expression and increased FGF signaling activity in Ext1 mutant lungs, suggesting a cell non-autonomous mechanism. Consistent with this, we observed reduced levels of SHH signaling which is responsible for suppressing Fgf10 expression. Moreover, reactivating SHH signaling in mutant lungs rescued the tip dilation phenotype and attenuated FGF signaling. Importantly, the reduced SHH signaling activity did not appear to be caused by decreased Shh expression or protein stability; instead, biologically active form of SHH proteins were reduced in both the Ext1 mutant epithelium and surrounding wild type mesenchymal cells. Together, our study highlights the epithelial HS as a key player for dictating SHH signaling critical for lung morphogenesis.

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“…PDGF signalling is thus regulated by both Nsulfation and 6-O sulfation. N-sulfation or some factor requiring N-sulfation has also been shown to be important in the developing mammary gland (Bush KT1 et al 2012).…”

Section: Discussionmentioning

confidence: 99%