Girding for migratory cues: roles of the Akt substrate Girdin in cancer progression and angiogenesis

Weng, Liang; Enomoto, Atsushi; Ishida-Takagishi, Maki; Asai, Naoya; Takahashi, Masahide

doi:10.1111/j.1349-7006.2010.01487.x

Cited by 21 publications

(33 citation statements)

References 58 publications

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“…The NT and coiled-coil domains of Daple include the putative oligomerisation domain 30,33 . That domain shows close similarities (54%) to that of Girdin, which we recently characterised as an actin-binding protein that promotes cell migration [34][35][36][37][38] . Notably, the CT domain of Daple lacks similarities to that of Girdin or any other known functional domain described previously, hinting that the distinctive function of Daple may be located within its CT domain.…”

Section: Daple Enhances the Activation Of Racmentioning

confidence: 84%

The Dishevelled-associating protein Daple controls the non-canonical Wnt/Rac pathway and cell motility

et al. 2012

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Dishevelled is the common mediator of canonical and non-canonical Wnt signalling pathways, which are important for embryonic development, tissue maintenance and cancer progression. In the non-canonical Wnt signalling pathway, the Rho family of small GTPases acting downstream of Dishevelled has essential roles in cell migration. The mechanisms by which the non-canonical Wnt signalling pathway regulates Rac activation remain unknown. Here we show that Daple (Dishevelled-associating protein with a high frequency of leucine residues) regulates Wnt5a-mediated activation of Rac and formation of lamellipodia through interaction with Dishevelled. Daple increases the association of Dishevelled with an isoform of atypical protein kinase C, consequently promoting Rac activation. Accordingly, Daple deficiency impairs migration of fibroblasts and epithelial cells during wound healing in vivo. These findings indicate that Daple interacts with Dishevelled to direct the Dishevelled/protein kinase λ protein complex to activate Rac, which in turn mediates the non-canonical Wnt signalling pathway required for cell migration.

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Section: Daple Enhances the Activation Of Racmentioning

confidence: 84%

The Dishevelled-associating protein Daple controls the non-canonical Wnt/Rac pathway and cell motility

et al. 2012

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“…Attenuated expression of RALGAPA2 leads to tumor invasion and metastasis of bladder cancer (21). Gridin regulates reorganization of the actin cytoskeleton and modulation of AKT activity, which ultimately result in cancer invasion and angiogenesis (30). Annexin A2, IQGAP1, and EPHA2 are closely associated with drug resistance.…”

Section: Discussionmentioning

confidence: 99%

Integrated Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) Quantitative Proteomic Analysis Identifies Galectin-1 as a Potential Biomarker for Predicting Sorafenib Resistance in Liver Cancer*

Yeh¹,

Hsu

Shao

et al. 2015

Molecular & Cellular Proteomics

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Sorafenib has become the standard therapy for patients with advanced hepatocellular carcinoma (HCC). Unfortunately, most patients eventually develop acquired resistance. Therefore, it is important to identify potential biomarkers that could predict the efficacy of sorafenib. To identify target proteins associated with the development of sorafenib resistance, we applied stable isotope labelling with amino acids in cell culture (SILAC)-based quantitative proteomic approach to analyze differences in protein expression levels between parental HuH-7 and sorafenib-acquired resistance HuH-7 (HuH-7 R ) cells in vitro, combined with an isobaric tags for relative and absolute quantitation (iTRAQ) quantitative analysis of HuH-7 and HuH-7 R tumors in vivo. In total, 2,450 quantified proteins were identified in common in SILAC and iTRAQ experiments, with 81 showing increased expression (>2.0-fold) with sorafenib resistance and 75 showing decreased expression (<0.5-fold). In silico analyses of these differentially expressed proteins predicted that 10 proteins were related to cancer with involvements in cell adhesion, migration, and invasion. Knockdown of one of these candidate proteins, galectin-1, decreased cell proliferation and metastasis in HuH-7 R cells and restored sensitivity to sorafenib. We verified galectin-1 as a predictive marker of sorafenib resistance and a downstream target of the AKT/mTOR/HIF-1␣ signaling pathway. In addition, increased galectin-1 expression in HCC patients' serum was associated with poor tumor control and low response rate. We also found that a high serum galectin-1 level was an independent factor associated with poor progression-free survival and overall survival. In conclusion, these results suggest that galectin-1 is a possible biomarker for predicting the response of HCC patients to treatment with sorafenib. As such, it may assist in the stratification of HCC and help direct personalized therapy. Molecular & Cellular

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“…We recently described another G␣-interacting protein, GIV (13), and showed that it is a GEF that activates G␣ subunits and mediates its biological functions via a defined motif (14) with structural similarity to the synthetic GEF peptide KB-752 (15). GIV is a metastasis-related protein (16) that enhances PI3K-Akt signaling and promotes macrophage, endothelial, epithelial, and tumor cell migration (17)(18)(19).…”

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confidence: 99%

G Protein Binding Sites on Calnuc (Nucleobindin 1) and NUCB2 (Nucleobindin 2) Define a New Class of Gαi-regulatory Motifs

Garcia‐Marcos

Kietrsunthorn

Wang

et al. 2011

Journal of Biological Chemistry

100

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Heterotrimeric G proteins are molecular switches modulated by families of structurally and functionally related regulators. GIV (G␣-interacting vesicle-associated protein) is the first nonreceptor guanine nucleotide exchange factor (GEF) that activates G␣ i subunits via a defined, evolutionarily conserved motif. Here we found that Calnuc and NUCB2, two highly homologous calcium-binding proteins, share a common motif with GIV for G␣ i binding and activation. Bioinformatics searches and structural analysis revealed that Calnuc and NUCB2 possess an evolutionarily conserved motif with sequence and structural similarity to the GEF sequence of GIV. Using in vitro pulldown and competition assays, we demonstrate that this motif binds preferentially to the inactive conformation of G␣ i1 and G␣ i3 over other G␣ subunits and, like GIV, docks onto the ␣3/switch II cleft. Calnuc binding was impaired when Lys-248 in the ␣3 helix of G␣ i3 was replaced with M, the corresponding residue in G␣ o , which does not bind to Calnuc. Moreover, mutation of hydrophobic residues in the conserved motif predicted to dock on the ␣3/switch II cleft of G␣ i3 impaired the ability of Calnuc and NUCB2 to bind and activate G␣ i3 in vitro. We also provide evidence that calcium binding to Calnuc and NUCB2 abolishes their interaction with G␣ i3 in vitro and in cells, probably by inducing a conformational change that renders the G␣ i -binding residues inaccessible. Taken together, our results identify a new type of G␣ i -regulatory motif named the GBA motif (for G␣-binding and -activating motif), which is conserved across different proteins throughout evolution. These findings provide the structural basis for the properties of Calnuc and NUCB2 binding to G␣ subunits and its regulation by calcium ions.

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Girding for migratory cues: roles of the Akt substrate Girdin in cancer progression and angiogenesis

Cited by 21 publications

References 58 publications

The Dishevelled-associating protein Daple controls the non-canonical Wnt/Rac pathway and cell motility

The Dishevelled-associating protein Daple controls the non-canonical Wnt/Rac pathway and cell motility

Integrated Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) Quantitative Proteomic Analysis Identifies Galectin-1 as a Potential Biomarker for Predicting Sorafenib Resistance in Liver Cancer*

G Protein Binding Sites on Calnuc (Nucleobindin 1) and NUCB2 (Nucleobindin 2) Define a New Class of Gαi-regulatory Motifs

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