ARAP3 inhibits peritoneal dissemination of scirrhous gastric carcinoma cells by regulating cell adhesion and invasion

Yagi, Ryoji; Tanaka, Masamitsu; Sasaki, Kazuki; Kamata, Reiko; Nakanishi, Yukihiro; Kanai, Yae; Sakai, Ryuichi

doi:10.1038/onc.2010.522

Cited by 29 publications

(24 citation statements)

References 24 publications

(26 reference statements)

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“…ARAP3 expression has been reported to slow cell migration, specifically, slowing peritoneal dissemination of cirrhous gastric carcinoma cells [48]. Our results show that glucose and serum deprivation causes a decrease in ARAP3 protein abundance, but an increase in gene expression was also observed.…”

Section: Discussionsupporting

confidence: 61%

“…However as there is a difference in the gene and protein expression data, we cannot say with certainty that this would be a negative effect of NR. Since the phosphorylation state of ARAP3 is implicated in the invasiveness of cancer [48], further phosphoproteomic profiling experiments will be conducted to determine if the phosphorylation state of ARAP3 is altered during NR.…”

Section: Discussionmentioning

confidence: 99%

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Nutrient restriction of glucose or serum results in similar proteomic expression changes in 3D colon cancer cell cultures

et al. 2016

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Nutrient restriction, also known as caloric restriction, has been extensively examined for its positive impact on lifespan, immune system boost, and aging. In addition, nutrient restriction is implicated in decreasing cancer initiation and progression. Given the phenotypic changes associated with nutrient restriction, we hypothesized significant protein expression alterations must be associated with caloric restriction. To compare the molecular and phenotypic changes caused by glucose restriction and fetal bovine serum (FBS) restriction there is need for an efficient model system. We establish three dimensional cell culture models, known as spheroids, in the HCT 116 colorectal cancer cell line as a high throughput model for studying the proteomic changes associated with nutrient restriction. Flow cytometry was used to assess apoptosis and autophagy levels in the spheroids under nutrient restriction. Isobaric tags for relative and absolute quantification (iTRAQ) and liquid chromatography tandem mass spectrometry were used to determine differential protein abundances between the nutrient restriction conditions. We identified specific proteins that have implications in cancer progression and metastasis that are differentially regulated by restriction of either glucose or serum. These proteins include the up regulation of sirtuin 1 (SIRT1) and protein inhibitor of activated STAT 1 (PIAS1) and down regulation of multi-drug resistance protein (MRP1) and Zinc finger and BTB domain-containing protein 7A (ZBTB7). The results indicate nutrient restriction causes lower apoptotic and higher autophagy rates in HCT 116 spheroids. In addition, proteins shown to be differentially regulated by both glucose and serum restriction were similarly regulated.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Nutrient restriction of glucose or serum results in similar proteomic expression changes in 3D colon cancer cell cultures

et al. 2016

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“…[64][65][66][67][68][69] ARAP3 has been reported to inhibit dissemination of scirrhous gastric cancer. 70 AGAPs are composed of a G-protein like, PH, Arf GAP and Ank repeat domains. AGAPs bind directly to clathrin adaptor proteins 71,72 and to muscarinic receptor, affecting its trafficking.…”

Section: Introductionmentioning

confidence: 99%

Allosteric properties of PH domains in Arf regulatory proteins

et al. 2016

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Pleckstrin Homology (PH) domains bind phospholipids and proteins. They are critical regulatory elements of a number enzymes including guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) for Ras-superfamily guanine nucleotide binding proteins such as ADP-ribosylation factors (Arfs). Recent studies have indicated that many PH domains may bind more than one ligand cooperatively. Here we discuss the molecular basis of PH domain-dependent allosteric behavior of 2 ADPribosylation factor exchange factors, Grp1 and Brag2, cooperative binding of ligands to the PH domains of Grp1 and the Arf GTPase-activating protein, ASAP1, and the consequences for activity of the associated catalytic domains.

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“…It is known that ARAP3 regulates many cell functions through its RhoGAP activity, such as formation of lamellipodia upon growth factor stimulation (11), development of angiogenesis in PI3K signaling pathway (12), and inhibition of peritoneal dissemination of scirrhous gastric carcinoma cells (13). Because Rap1-GTP can up-regulate the RhoGAP activity of ARAP3, the role of ARAP3 in downstream Rap1-GTP cell processes is RhoGAP-dependent.…”

mentioning

confidence: 99%

Structural Basis for the Specific Recognition of RhoA by the Dual GTPase-activating Protein ARAP3

Bao

Wang

et al. 2016

Journal of Biological Chemistry

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ARAP3 (Arf-GAP with Rho-GAP domain, ANK repeat, and PH domain-containing protein 3) is unique for its dual specificity GAPs (GTPase-activating protein) activity for Arf6 (ADPribosylation factor 6) and RhoA (Ras homolog gene family member A) regulated by phosphatidylinositol 3,4,5-trisphosphate and a small GTPase Rap1-GTP and is involved in regulation of cell shape and adhesion. However, the molecular interface between the ARAP3-RhoGAP domain and RhoA is unknown, as is the substrates specificity of the RhoGAP domain. In this study, we solved the crystal structure of RhoA in complex with the RhoGAP domain of ARAP3. The structure of the complex presented a clear interface between the RhoGAP domain and RhoA. By analyzing the crystal structure and in combination with in vitro GTPase activity assays and isothermal titration calorimetry experiments, we identified the crucial residues affecting RhoGAP activity and substrates specificity among RhoA, Rac1 (Ras-related C3 botulinum toxin substrate 1), and Cdc42 (cell division control protein 42 homolog).

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ARAP3 inhibits peritoneal dissemination of scirrhous gastric carcinoma cells by regulating cell adhesion and invasion

Cited by 29 publications

References 24 publications

Nutrient restriction of glucose or serum results in similar proteomic expression changes in 3D colon cancer cell cultures

Nutrient restriction of glucose or serum results in similar proteomic expression changes in 3D colon cancer cell cultures

Allosteric properties of PH domains in Arf regulatory proteins

Structural Basis for the Specific Recognition of RhoA by the Dual GTPase-activating Protein ARAP3

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