Regulation of Notch Signaling Through Intracellular Transport

Conner, S. D.

doi:10.1016/bs.ircmb.2015.12.002

Cited by 33 publications

(22 citation statements)

References 125 publications

(171 reference statements)

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“…Notch signaling pathway (Figure 3 ) plays an important role in intercellular communication and cell fate determination during embryogenesis and in adult cells [ 40 ]. The pathway includes four receptors (Notch1∼Notch4) and five ligands that regulate expression of multiple target genes [ 41 ].…”

Section: Molecular Mechanisms Of Bladder Cancer Stem Cellsmentioning

confidence: 99%

Bladder cancer stem cells: clonal origin and therapeutic perspectives

Lin

Yang

et al. 2017

Oncotarget

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In this article, we review the origin and therapeutic perspectives of bladder cancer stem cells (BCSCs), which are integral to the initiation, high recurrence and chemoresistance of bladder cancer. BCSCs are heterogenous and originate from multiple cell types, including urothelial stem cells and differentiated cell types, including basal, intermediate stratum and umbrella cells. Cell surface markers, including CD44, CD67LR, EMA, ALDH1A1 and BCMab1, are used to identify and isolate BCSCs. The Hedgehog, Notch, Wnt and JAK-STAT signaling pathways play key roles in maintaining the stemness, self-renewal and proliferative potential of BCSCs. High expression of ABC transporters, acetaldehyde dehydrogenase, antioxidants and apoptosis resistance proteins in BCSCs play a critical role in chemoresistance. Consequently, a greater understanding of the biology of BCSCs will be important for identifying effective therapeutic targets to improve clinical outcomes for bladder cancer patients.

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Section: Molecular Mechanisms Of Bladder Cancer Stem Cellsmentioning

confidence: 99%

Bladder cancer stem cells: clonal origin and therapeutic perspectives

Lin

Yang

et al. 2017

Oncotarget

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“…The Notch pathway must be tightly controlled, given that signaling defects can lead to disease ( Joutel et al , 1996 ; Rangarajan et al , 2001 ; Weng et al , 2004 ). Emerging evidence implicates a critical role for endosomal transport genes in controlling Notch activity ( Baron, 2012 ; Kandachar and Roegiers, 2012 ; Conner, 2016 ). While it is likely that cells possess mechanisms to regulate Notch activity in response to a dynamic extracellular environment, it remains unclear if extracellular cues can directly impact Notch transport decisions that lead to changes in signaling capacity.…”

Section: Introductionmentioning

confidence: 99%

Glycogen synthase kinase 3β inhibition enhances Notch1 recycling

Conner

2018

MBoC

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“…The activity within each gut subregion is strongly impacted by distinct self-renewing intestinal stem cells (ISCs) (Micchelli and Perrimon, 2006;Ohlstein and Spradling, 2006) whose daughter cells differentiate in response to a high Notch signal into nutrient-processing enterocytes (ECs), or in the presence of low intracellular Notch activity into multiple types of hormone-secreting enteroendocrine cells (ee's) (Ohlstein and Sprading, 2007;Guo and Ohlstein, 2015). Notch signaling is largely regulated by its ligand, the transmembrane protein Delta, whose activity is influenced by factors that impact the trafficking, recycling and turnover within endosomal vesicles of both Delta and Notch itself (Seugnet et al, 1997;Conner, 2016). In the mammalian intestine, Notch signaling also specifies enterocytes and enteroendocrine cells (Demitrack and Samuelson, 2016).…”

Section: Introductionmentioning

confidence: 99%

Dietary lipids modulate Notch signaling and influence adult intestinal development and metabolism inDrosophila

Obniski

Sieber

Spradling

2018

Preprint

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Tissue homeostasis is a complex balance of developmental signals and environmental cues that dictate stem cell function. However, it remains poorly understood how nutrients interface with developmental pathways. Using the Drosophila midgut as a model we found that during the first four days of adult life, dietary lipids including cholesterol, determine how many enteroendocrine (ee) cells differentiate and persist in the posterior midgut where lipids are preferentially absorbed. The nuclear hormone receptor Hr96 which functions to control sterol trafficking, storage, and utilization, is required for sterol-mediated changes in ee number. Dietary cholesterol influences new intestinal epithelial cell differentiation from stem cells by altering the level and persistance of Notch signaling. Exogenous lipids modulate signaling by changing the stability of the Delta ligand and Notch intracellular domain and their trafficking in endosomal vesicles. Lipid-modulated Notch signaling occurs in other nutrient-dependent tissuessuch as the ovary, suggesting that Delta trafficking in many cells is sensitive to cellular sterol levels. These diet-mediated alterations in ee number in young animals contribute to a metabolic program adapted to the prevailing nutrient environment that persists after the diet changes. A low sterol diet also slows the proliferation of enteroendocrine tumors initiated by disruptions in the Notch pathway. These studies show that a specific dietary nutrient can modify a key intercellular signaling pathway to shift stem cell differentiation and cause lasting changes in tissue structure and physiology.3

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Regulation of Notch Signaling Through Intracellular Transport

Cited by 33 publications

References 125 publications

Bladder cancer stem cells: clonal origin and therapeutic perspectives

Bladder cancer stem cells: clonal origin and therapeutic perspectives

Glycogen synthase kinase 3β inhibition enhances Notch1 recycling

Dietary lipids modulate Notch signaling and influence adult intestinal development and metabolism inDrosophila

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