Cholesterol Regulates Syntaxin 6 Trafficking at trans-Golgi Network Endosomal Boundaries

Reverter, Meritxell; Rentero, Carles; García-Melero, Ana; Hoque, Monira; Muga, Sandra Vilà de; Álvarez-Guaita, Anna; Conway, James R. W.; Wood, Peta; Cairns, Rose; Lykopoulou, Lilia; Grinberg, Daniel; Vilageliu, Lluı̈sa; Bosch, Marta; Heeren, Joerg; Blasi, Juan; Timpson, Paul; Pol, Albert; Tebar, Francesc; Murray, Rachael Z.; Grewal, Thomas; Enrich, Carlos

doi:10.1016/j.celrep.2014.03.043

Cited by 95 publications

(109 citation statements)

References 71 publications

Supporting

Mentioning

106

Contrasting

Order By: Relevance

“…The majority of late-endosome-derived cholesterol is then delivered to the plasma membrane, while some of it is transported to the ER to enable feedback control or undergoes esterification for storage in lipid droplets in the form of cholesteryl esters. The routes and mechanisms by which late endosome-originating cholesterol reaches the plasma membrane are not clear, but as shown by our laboratory (Cubells et al, 2007;Reverter et al, 2014) and others (Kanerva et al, 2013;Urano et al, 2008), might involve transport through the ER, the transGolgi network (TGN) and recycling endosomes (Fig. 1A).…”

Section: Intracellular Trafficking Of Cholesterolmentioning

confidence: 99%

“…Niemann Pick C1 protein (NPC1) and Niemann Pick type C2 protein homolog (NPC2) bind to late-endosome-associated cholesterol and facilitate its export from late endosomes (Ikonen, 2006;Vance and Karten, 2014). Mutations in the genes encoding NPC1 or NPC2 inhibit the egress of cholesterol from late endosomes (Klein et al, 2006) and reduce its delivery to the Golgi, plasma membrane and recycling endosomes (Cubells et al, 2007;Kanerva et al, 2013;Reverter et al, 2014;Urano et al, 2008). Together, this triggers a dysfunction of membrane trafficking, which is associated with cardiovascular, neurological and lysosomal storage diseases (Cortes et al, 2013;De Matteis and Luini, 2011;Ikonen, 2006;Maxfield and Tabas, 2005).…”

Section: Intracellular Trafficking Of Cholesterolmentioning

confidence: 99%

See 1 more Smart Citation

Role of cholesterol in SNARE-mediated trafficking on intracellular membranes

Enrich

Rentero

Hierro

et al. 2015

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

The cell surface delivery of extracellular matrix (ECM) and integrins is fundamental for cell migration in wound healing and during cancer cell metastasis. This process is not only driven by several soluble NSF attachment protein (SNAP) receptor (SNARE) proteins, which are key players in vesicle transport at the cell surface and intracellular compartments, but is also tightly modulated by cholesterol. Cholesterol-sensitive SNAREs at the cell surface are relatively well characterized, but it is less well understood how altered cholesterol levels in intracellular compartments impact on SNARE localization and function. Recent insights from structural biology, protein chemistry and cell microscopy have suggested that a subset of the SNAREs engaged in exocytic and retrograde pathways dynamically 'sense' cholesterol levels in the Golgi and endosomal membranes. Hence, the transport routes that modulate cellular cholesterol distribution appear to trigger not only a change in the location and functioning of SNAREs at the cell surface but also in endomembranes. In this Commentary, we will discuss how disrupted cholesterol transport through the Golgi and endosomal compartments ultimately controls SNARE-mediated delivery of ECM and integrins to the cell surface and, consequently, cell migration.

show abstract

Section: Intracellular Trafficking Of Cholesterolmentioning

confidence: 99%

Section: Intracellular Trafficking Of Cholesterolmentioning

confidence: 99%

Role of cholesterol in SNARE-mediated trafficking on intracellular membranes

Enrich

Rentero

Hierro

et al. 2015

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

show abstract

“…The other is by phosphorylating the relative kinases, including focal adhesion kinases (FAKs), proto-oncogene tyrosine-protein kinase (Src)-family kinases (SFKs) and integrin-linked kinase (ILK), to activate or cooperate with the other cell signaling pathways (1,4). Additionally, integrin clustering on the cell surface and trafficking from the endosomes may affect the ligand affinity and quantity of the protein on cell surface (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

β1 and β3 integrins in breast, prostate and pancreatic cancer: A novel implication (Review)

et al. 2018

View full text Add to dashboard Cite

Abstract.Integrins are transmembrane glycoproteins that consist of an α and a β subunit. Specific integrin heterodimers preferentially bind to distinct extracellular matrix (ECM) proteins to affect the characteristics of cells or the components of the ECM. Among the different integrins, β1 and β3 integrins serve essential roles in the progression of different cancer-associated processes, including the initiation, proliferation, survival, migration and invasion. Furthermore, previous studies have revealed a ratio between these two integrins in cancer cells, which also demonstrated that the functions of these two integrins are paradoxical. This indicated that the proliferation and metastasis of cancer cells are not always parallel and may be considered independently maintained. Additionally, the present review may assist in understanding certain aspects of cancer, and in making clinical decisions in a novel and more comprehensive manner. IntroductionIntegrins are transmembrane glycoproteins that consist of an α subunit and a β subunit. A total of eight different β subunits may dimerize, in limited combinations, with 18α subunits to form ≥24 distinct integrins (1,2). Specific integrin heterodimers preferentially bind to distinct extracellular matrix (ECM) proteins. Integrins may bind the ligands in ECM directly, including fibronectin and laminin, to affect the characteristics of cells or the components of ECM. Regarding cancer cells, integrins serve roles in numerous aspects, including proliferation, survival, migration and invasion (1).Integrins primarily affect cells in two ways, the first is through binding with proteins directly, including talin, vinculin and filamin, which may regulate the actin cytoskeleton of cells (3). The other is by phosphorylating the relative kinases, including focal adhesion kinases (FAKs), proto-oncogene tyrosine-protein kinase (Src)-family kinases (SFKs) and integrin-linked kinase (ILK), to activate or cooperate with the other cell signaling pathways (1,4). Additionally, integrin clustering on the cell surface and trafficking from the endosomes may affect the ligand affinity and quantity of the protein on cell surface (5-7).Among the different integrins, β1 and β3 integrins serve essential roles in the progression of different types of cancer (1,2). Furthermore, previous studies investigating the association between these two integrins have demonstrated many different perspectives (8-11), together providing a novel and more comprehensive understanding of cancer. Functions of β1 integrin in cancerIn tumors, the β1 subunit of integrin may combine with different α subunits, including α4, α5 and α2, to affect the characteristics of cancer cells, and the progression of tumors (1). The primary function of β1 integrin is to form focal adhesion between cancer cells and ECM. This adhesion is the basis for the survival of cancer cells and is also associated with their migratory and metastatic capabilities (2). There are series of proteins in the cytoplasm, including talin, kindlin and ILK, ...

show abstract

“…This dietary habit causes increased levels of cholesterol and low-density lipoproteins (LDL) in the blood, which can eventually develop into hyperlipidemia. According to recent data, hyperlipidemia is one factor contributing to the increased incidence of colorectal cancer (3,4) as high levels of cholesterol and LDL can enhance cancer growth and metastasis (5,6). Statin compounds are the most commonly used drugs to reduce the levels of cholesterol and LDL; therefore, using statins to prevent cancer is a recommended treatment for patients with hyperlipidemia.…”

Section: Introductionmentioning

confidence: 99%

Synergistic inhibition of colon cancer cell growth by a combination of atorvastatin and phloretin

Zhou

Zheng

et al. 2017

Oncol Lett

View full text Add to dashboard Cite

Abstract. Atorvastatin (ATST), a drug commonly used to reduce the levels of cholesterol and low-density lipoproteins, is a prospective agent for the prevention of colorectal cancer in patients with hyperlipidemia. ATST in combination with functional components is a promising strategy for cancer chemoprevention. In the present study, the growth inhibitory effect of ATST combined with phloretin (PT) on SW620 and HCT116 colon cancer cells was investigated. The results of MTT assays indicated that the combination of PT and ATST markedly reduced cell survival in both cell lines compared with PT or ATST treatment administered individually. The interaction indexes between PT and ATST, which were used to analyze their interaction pattern, were computed by the median-effect equation. The interaction indexes of each PT and ATST concentration pair were <1.0, which indicated a strong synergistic effect between the two compounds. The data obtained by flow cytometry and western blot analysis of cleaved-poly (ADP-ribose) polymerase indicated a synergistic effect resulted in apoptosis and cell cycle arrest at the G 2 /M checkpoint. Furthermore, combined treatment with PT and ATST markedly downregulated the expression of cyclin B and upregulated the expression of phospho-cdc2 and Myt1, which suggested that the activation of cdc2 was downregulated. This combined treatment strategy enhanced the anti-cancer activity of ATST at a relatively low dosage and suggested a possible method of preventing colorectal cancer in patients with hyperlipidemia.

show abstract

Cholesterol Regulates Syntaxin 6 Trafficking at trans-Golgi Network Endosomal Boundaries

Cited by 95 publications

References 71 publications

Role of cholesterol in SNARE-mediated trafficking on intracellular membranes

Role of cholesterol in SNARE-mediated trafficking on intracellular membranes

β1 and β3 integrins in breast, prostate and pancreatic cancer: A novel implication (Review)

Synergistic inhibition of colon cancer cell growth by a combination of atorvastatin and phloretin

Contact Info

Product

Resources

About