Role of Scaffold Protein Afadin Dilute Domain-interacting Protein (ADIP) in Platelet-derived Growth Factor-induced Cell Movement by Activating Rac Protein through Vav2 Protein

Fukumoto, Yuri; Kurita, Souichi; Takai, Yoshimi; Ogita, Hisakazu

doi:10.1074/jbc.m111.308858

Cited by 20 publications

(24 citation statements)

References 49 publications

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“…More recently it has been shown that PDGF activates Src kinase, which in turn leads to activation of Rac31. In this context, an afadin-binding protein, afadin dilute domain-interacting protein (ADIP), interacted with Vav2, a GDP/GTP exchange factor for Rac, in a Src phosphorylation-dependent manner32. These results indicate that ADIP may be involved in PDGF-induced cell movement through Src/Rac signalling pathway and will be a potential target for α-Syn.…”

Section: Discussionmentioning

confidence: 99%

Impairment of PDGF-induced chemotaxis by extracellular α-synuclein through selective inhibition of Rac1 activation

Okada

Hirai

Badawy

et al. 2016

Sci Rep

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Parkinson’s disease (PD) is characterized by α-synuclein (α-Syn)-positive intracytoplasmic inclusions, known as Lewy bodies. Although it is known that extracellular α-Syn is detected in the plasma and cerebrospinal fluid, its physiological significance remains unclear. Here, we show that extracellular α-Syn suppresses platelet-derived growth factor (PDGF)-induced chemotaxis in human neuroblastoma SH-SY5Y cells. The inhibitory effect was stronger in the mutant α-Syn(A53T), found in hereditary PD, and the degree of inhibition was time-dependent, presumably because of the oligomerization of α-Syn. PDGF-induced activation of Akt or Erk was not influenced by α-Syn(A53T). Further studies revealed that α-Syn(A53T) inhibited PDGF-induced Rac1 activation, whereas Cdc42 activation remained unaffected, resulting in unbalanced actin filament remodeling. These results shed light on the understanding of pathological as well as physiological functions of extracellular α-Syn in neuronal cells.

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Section: Discussionmentioning

confidence: 99%

Impairment of PDGF-induced chemotaxis by extracellular α-synuclein through selective inhibition of Rac1 activation

Okada

Hirai

Badawy

et al. 2016

Sci Rep

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“…Its homologous gene in rodents is ADIP (afadin DIL domain-interacting protein), the amino acid sequence of ADIP protein in mouse and rat showed 88% and 87% identity with SSX2IP protein, respectively. ADIP localized in cell-cell adherens junctions, and it can promote cell mobility by activating Rac1 through Vav2 [41], [42]. It is speculated that SSX2IP could promote cell motility, invasion and metastasis through activating Rac1.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Silencing of miR-338-3p Contributes to Tumorigenicity in Gastric Cancer by Targeting SSX2IP

Chen

et al. 2013

PLoS ONE

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MicroRNA has been recently recognized as playing a prominent role in tumorigenesis and metastasis. Here, we report that miR-338-3p was epigenetically silenced in gastric cancer, and its down-regulation was significantly correlated with gastric cancer clinicopathological features. Strikingly, restoring miR-338-3p expression in SGC-7901 gastric cancer cells inhibited proliferation, migration, invasion and tumorigenicity in vitro and in vivo, at least partly through inducing apoptosis. Furthermore, we demonstrate the oncogene SSX2IP is a target of miR-338-3p. We propose that miR-338-3p functions as a tumor suppressor in gastric cancer, and the methylation status of its CpG island could serve as a potential diagnostic marker for gastric cancer.

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“…On the other hand, ADIP has been shown to promote cell movement by regulating the activation of Rac1 [16]. Rac1 belongs to the Rho family and the Ras superfamily of small GTP-binding proteins, and it is an important regulator which connects membrane surface receptors and actin cytoskeleton and plays a role of molecular switch.…”

Section: Discussionmentioning

confidence: 99%

“…Cytologically, ADIP localizes at cell-cell adherens junctions and promotes cell migration by activating Rac protein through Vav2 [15,16]. All of the above characteristics are closely related to the adhesion capacity and metastatic characteristics.…”

Section: Introductionmentioning

confidence: 99%

SSX2IP promotes metastasis and chemotherapeutic resistance of hepatocellular carcinoma

Lin

Zhang

et al. 2013

J Transl Med

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BackgroundSynovial sarcoma, X breakpoint 2 interacting protein (SSX2IP), which has been identified as an acute myeloid leukemia associated antigen, is a potential target for leukemia immunotherapy. In rodents, its homologous gene, ADIP, plays an important role in the regulation of cell adhesion and migration, underlying its potential role in promoting metastasis of other cancers.MethodsTo investigate the correlation between the expression level of SSX2IP and the clinicopathologic factors of hepatocellular carcinoma (HCC), 53 cases were studied by qPCR and statisted. To directly testing SSX2IP’s contribution to HCC in animal models, 45 nude mice were enrolled in peritoneal spreading and liver metastasis models. For the migration and invasion assays, cell culture experiments were performed using QCMTM 24-Well Colorimetric Migration Assay Kit and Cell Invasion Assay Kit (Millipore). Moreover we examined the influence of SSX2IP overexpression on the chemosensitivity of hepatocellular carcinoma cells to two most common chemotherapy drugs (5-Fu and CDDP) using Cell counting kit-8 (CCK-8). The chemotherapeutic drugs sensitivity was evaluated by IC50 parameter.ResultsStatistical analysis of clinical cases revealed that the SSX2IP high expression group had inclinations towards larger tumor size, more tumor thrombus and shorter survival period, implying a strong correlation between the expression level of SSX2IP and HCC tumorigenesis. Consistently in abdominal cavity metastasis and liver metastasis models of immune-deficient mice, SSX2IP was able to promote the metastasis of hepatoma cells. At the cytological level, SSX2IP stimulates the wound healing, metastasis and invasion of hepatoma cells, and reduces the sensitivity of hepatoma cells to 5-Fu and CDDP.ConclusionsOur results showed that SSX2IP promotes the development and metastasis of hepatocellular carcinoma and contributes to the drug resistance of hepatoma cells, suggesting that SSX2IP is expected to become a new diagnostic and prognostic marker and a new target of the treatment of hepatocellular carcinoma.

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Role of Scaffold Protein Afadin Dilute Domain-interacting Protein (ADIP) in Platelet-derived Growth Factor-induced Cell Movement by Activating Rac Protein through Vav2 Protein

Cited by 20 publications

References 49 publications

Impairment of PDGF-induced chemotaxis by extracellular α-synuclein through selective inhibition of Rac1 activation

Impairment of PDGF-induced chemotaxis by extracellular α-synuclein through selective inhibition of Rac1 activation

Epigenetic Silencing of miR-338-3p Contributes to Tumorigenicity in Gastric Cancer by Targeting SSX2IP

SSX2IP promotes metastasis and chemotherapeutic resistance of hepatocellular carcinoma

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