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Characteristics, Events, and Stages in Tumorigenesis
Published in Franklyn De Silva, Jane Alcorn, The Elusive Road Towards Effective Cancer Prevention and Treatment, 2023
Franklyn De Silva, Jane Alcorn
Microvesicles are produced from the plasma membrane through direct outward budding (and fission) with subsequent release into the extracellular space [830, 857, 896]. Membrane lipid curvature plays an important role for either inward-budding vesicle formation within the endocytic system (exosomes) or an outward-budding vesicle formation at the plasma membrane (microvesicles) [831]. Some of the biogenetic mechanisms involved include flippase, flippase and scramblase (TMEM16F), amino-phospholipid translocases, ARF6, membrane curvature, cytoskeleton, and asymmetric movement of phosphatidylserine [769, 840, 897–900]. From plasma membranes of prostate and breast cancer cells, the shedding of cancer-derived MVs is attributed to the ADP-ribosylation factor 6 (ARF6) that is enriched in MVs [851, 901]. EVs, (especially exosomes), have been identified as major modes by which cells interact with each other, including stromal cells, within the tumor microenvironment [849].
Intra-cytoplasmic Cytokine Staining (ICS): Optimizing antigen stimulation for measuring M. tuberculosis-specific T cell response
Published in Ade Gafar Abdullah, Isma Widiaty, Cep Ubad Abdullah, Medical Technology and Environmental Health, 2020
A cytokine secretion inhibitor is often used in most protocols of ICS to trap the cytokine within the cells. The proposed mechanism of Brefeldin A is inhibition some of proteins that activate ADP-ribosilation factors (Arf), which is critical for vesicular transport between endoplasmic reticulum and the Golgi (Chardin & McCormick 1999). Cytokine secretion inhibitors seem to be time and cytokine dependent. For example, another cytokine inhibitor, namely Monesin, in ICS decreased detection of IL-4 within cells (Smith et al. 2015), but the shorter incubation of Monesin improved the detection of IL-10 (Muris et al. 2012). The incubation of Brefeldin A for 3.5 hours (Muflihah et al. 2018) or less than 12 hours is for practicality (Miguel et al. 2012) and avoiding cell toxicity. Our work showed that prolonged incubation of Brefeldin A up to 18 hours improved the frequency (Figure 1) and functionality of T cells secreting IFN-γ, TNF, and IL2 (Figure 2B).
TRPML Subfamily of Endolysosomal Channels
Published in Bruno Gasnier, Michael X. Zhu, Ion and Molecule Transport in Lysosomes, 2020
Nicholas E. Karagas, Morgan A. Rousseau, Kartik Venkatachalam
Given the physical interactions between TRPML1 and TRPML2, it stands to reason that the latter protein also localizes to late-endosomes (Venkatachalam et al., 2006). In addition, TRPML2 has been detected in long tubulovesicular compartments associated with GTPase ADP-ribosylation factor-6 (Arf-6) (Karacsonyi et al., 2007; Radhakrishna and Donaldson, 1997). Indeed, activation of Arf-6 has been shown to cause accumulation of TRPML2 in tubulovesicular structures where it colocalizes with major histocompatibility complex I and glycosylphosphatidylinositol-anchored proteins (Karacsonyi et al., 2007). Interactions with TRPML1 drive TRPML3 to the endolysosomal membrane (Venkatachalam et al., 2006). When overexpressed alone in cell culture models, murine TRPML3-YFP was found localized to the endoplasmic reticulum (ER) (Venkatachalam et al., 2006). Only upon coexpression with TRPML1 or TRPML2, which possess endolysosomal targeting motifs, was TRPML3 delivered to the vesicles, yet again pointing to a hierarchical relationship between the channels. TRPML3 does appear to exhibit the greatest diversity in subcellular compartments. In addition to localizing to endolysosomal compartments, TRPML3 has also been shown to reside in the plasma membrane, early endosomes, and autophagosomal membranes (Kim et al., 2009; Martina et al., 2009; Miao et al., 2015).
ADP Ribosylation Factor 6 Relieves Airway Inflammation and Remodeling by Inhibiting Ovalbumin Induced-Epithelial Mesenchymal Transition in Experimental Asthma, Possibly by Regulating of E2F Transcription Factor 8
Published in Immunological Investigations, 2023
Dongdong Dou, Meirong Bi, Xiuyun Li, Nan Zhang, Mi Xu, Aili Guo, Feng Li, Weiwei Zhu
ADP-ribosylation factor 6 (ARF6) belongs to the ARF family of small GTPases and is involved in the regulation of membrane trafficking and structural and cytoskeletal dynamic (Donaldson and Jackson 2011). ARF6 is commonly expressed in various types of normal cells (including lungs) and is involved in the development and progression of various human diseases (Donaldson and Honda 2005; Schweitzer et al. 2011). Studies of AFR6 have focused on its key role in cell motility. AFR6 has been reported to be overexpressed in different cancer types and promotes cell adhesion, invasion, and metastasis (Hashimoto et al. 2004, 2016; Sabe 2003). In addition, ARF6 is involved in the endocytosis of E-cadherin, an intercellular adhesion molecule, which is essential for the acquisition of a mesenchymal phenotype. A previous study has shown that AFR6 is closely related to EMT. ARF6 disrupts cell junctions mediated by E-cadherin and inhibits EMT in head and neck cancer (Matsumoto et al. 2017). In pancreatic cancer, ARF6 up-regulated the expression of E-cadherin to promote fibrosis (Tsutaho et al. 2020). A recent study reported that the inhibition of AFR6 could attenuate ovalbumin (OVA)-induced asthma by inhibiting inflammation (Lee et al. 2021), however, its role in airway remodeling and EMT remains unclear.
Identification of novel genes by targeted exome sequencing in Retinoblastoma
Published in Ophthalmic Genetics, 2022
Shilpa Bisht, Bhavna Chawla, Amit Kumar, Viswanathan Vijayan, Manoj Kumar, Pradeep Sharma, Rima Dada
ARL11 encodes for a tumor suppressor gene related to the ADP-ribosylation factor (ARF) family of proteins (57). ARL11 protein plays an essential role in apoptosis in a caspase-dependent manner. Polymorphisms in ARL11 are found to be associated with some forms of familial cancers (58). Down-regulation of ARL11 expression in several sporadic lung cancer and ovarian tumors attributed to promoter methylation and loss of heterozygosity (LOH) at the ARL11 locus (57). Although the direct role of ARL11 mutation has not been described in RB pathogenesis, but in our study, we have found ARL11: g.2595G>A (nonsense mutation) in 4 RB patients which showed a significant contribution of the loss-of-function of tumor suppressor genes present in the 13q14.2 (location of RB1 tumor suppressor gene also) region. The actual mechanism of how ARL11 loss-of-function might contribute to RB progression is not known. But we might predict that ARL11 mediates its function through regulation of its downstream target genes (ADAM17, HIF1AN, IL17RD, and ALDH3A2) that have important role on tumorigenesis regulation. Hence, further extensive studies are required to determine the role of other genes present in the 13q14.2 locus so as to determine their essential functions in RB pathogenesis.
Clinical implication and immunological characterisation of the ARF-GEF family member CYTH4 in ovarian cancer
Published in Autoimmunity, 2020
Qinyi Zhang, Qingying Wang, Sufang Wu, Jiawen Zhang
The ADP-ribosylation factor (ARF) family GTPases are critical regulators of cellular signalling pathways involved in most cellular processes, including membrane trafficking, metabolism and transcriptional regulation, affecting cell division, apoptosis and motility [3,4]. ARF proteins require GTP exchange factors (GEFs) to accelerate nucleotide exchange and exert their biological activity through GTP-dependent recruitment of effectors [5–7]. Activating ARF-GEFs was tightly modulated by various mechanisms that impact their catalytic activity or membrane association, and dysregulation of ARF-GEFs has been reported to participate in tumorigenesis and progression [6,8,9]. For instance, IQSEC1 (also known as BRAG2, GEP100) regulates EGFR signalling to active ARF6 and induces metastasis and malignancy of breast cancer [10,11]. ARFGEF1 modulates the activity of miR-215 and controls epithelial-mesenchymal transition (EMT) in thyroid cancer [12]. Cytohesin family proteins CYTH1 and CYTH3 regulate cancer cell growth, invasion and migration [13–15]. However, the role of ARF-GEF family members in ovarian cancer is still poorly understood.