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https://www.readbyqxmd.com/read/28618949/iq-domain-gtpase-activating-protein-1-promotes-the-malignant-phenotype-of-invasive-ductal-breast-carcinoma-via-canonical-wnt-pathway
#1
Huan-Yu Zhao, Yang Han, Jian Wang, Lian-He Yang, Xiao-Ying Zheng, Jiang Du, Guang-Ping Wu, En-Hua Wang
IQ-domain GTPase-activating protein 1 is a scaffolding protein with multidomain which plays a role in modulating dishevelled (Dvl) nuclear translocation in canonical Wnt pathway. However, the biological function and mechanism of IQ-domain GTPase-activating protein 1 in invasive ductal carcinoma (IDC) remain unknown. In this study, we found that IQ-domain GTPase-activating protein 1 expression was elevated in invasive ductal carcinoma, which was positively correlated with tumor grade, lymphatic metastasis, and poor prognosis...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28603713/dishevelled-paralogs-in-vertebrate-development-redundant-or-distinct
#2
REVIEW
Marc Gentzel, Alexandra Schambony
Dishevelled (DVL) proteins are highly conserved in the animal kingdom and are important key players in β-Catenin-dependent and -independent Wnt signaling pathways. Vertebrate genomes typically comprise three DVL genes, DVL1, DVL2, and DVL3. Expression patterns and developmental functions of the three vertebrate DVL proteins however, are only partially redundant in any given species. Moreover, expression and function of DVL isoforms have diverged between different vertebrate species. All DVL proteins share basic functionality in Wnt signal transduction...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28595998/targeting-of-cxxc5-by-a-competing-peptide-stimulates-hair-re-growth-and-wound-induced-hair-neogenesis
#3
Soung-Hoon Lee, Seol Hwa Seo, Dong-Hwan Lee, Long-Quan Pi, Won-Soo Lee, Kang-Yell Choi
The Wnt/β-catenin pathway has been implicated in hair follicle development and hair regeneration in adults. We discovered that CXXC-type zinc finger protein 5 (CXXC5) is a negative regulator of the Wnt/β-catenin pathway involved in hair re-growth and wound-induced hair follicle neogenesis (WIHN) via an interaction with Dishevelled (Dvl). CXXC5 was up-regulated in miniaturized hair follicles and arrector pili muscles in human balding scalps. The inhibitory effects of CXXC5 on alkaline phosphatase activity and cell proliferation were demonstrated using human hair follicle dermal papilla cells...
June 5, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28589433/overexpression-of-dishevelled-2-is-involved-in-tumor-metastasis-and-is-associated-with-poor-prognosis-in-hepatocellular-carcinoma
#4
C Zhang, C Li, X Chen, Y Zhou, B Yin, R Ni, Y Zhang, J Liu
PURPOSE: Although hepatocellular carcinoma (HCC) is one of the most common malignant tumors, its molecular mechanism is still unknown. Dishevelled 2 (Dvl2) is one of the downstream targets of non-canonical Wnt signaling, which has been demonstrated to be of great importance in the progression of cancers. Nevertheless, the expression mechanisms and physiological significance of Dvl2 in HCC remain unclear. METHODS: Western blotting and immunohistochemistry were used to measure Dvl2 protein expression in HCC and adjacent normal tissues of 101 patients...
June 6, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28548684/origins-of-anterior-posterior-polarity-by-localized-activation-of-disheveled
#5
Jeff Chieh-Fu Peng, Lingyu Wang, Athula H Wikramanayake
Most animal eggs have a primordial polarity, termed the animal-vegetal (AV) axis, that frequently predicts the anterior-posterior (AP) axis of the embryo and adult. Transformation of the AV polarity of the egg to the AP polarity of the embryo in many species is mediated by the localized activation of canonical Wnt (cWnt) signaling in vegetal blastomeres by maternal determinants. In the sea urchin egg, cWnt signal transduction is facilitated by localized "activation" of the Disheveled protein, a central regulator of Wnt signaling...
May 26, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28546512/wnt5a-promotes-frizzled-4-signalosome-assembly-by-stabilizing-cysteine-rich-domain-dimerization
#6
Zachary J DeBruine, Jiyuan Ke, Kaleeckal G Harikumar, Xin Gu, Peter Borowsky, Bart O Williams, Wenqing Xu, Laurence J Miller, H Eric Xu, Karsten Melcher
Wnt/β-catenin signaling is activated when extracellular Wnt ligands bind Frizzled (FZD) receptors at the cell membrane. Wnts bind FZD cysteine-rich domains (CRDs) with high affinity through a palmitoylated N-terminal "thumb" and a disulfide-stabilized C-terminal "index finger," yet how these binding events trigger receptor activation and intracellular signaling remains unclear. Here we report the crystal structure of the Frizzled-4 (FZD4) CRD in complex with palmitoleic acid, which reveals a CRD tetramer consisting of two cross-braced CRD dimers...
May 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28543074/wwc3-regulates-the-wnt-and-hippo-pathways-via-dvls-and-lats1-to-suppress-lung-cancer-invasion-and-metastasis
#7
Qiang Han, Xuyong Lin, Xiupeng Zhang, Guiyang Jiang, Yong Zhang, Yuan Miao, Xuezhu Rong, Xiaoying Zheng, Yong Han, Xu Han, Jingjing Wu, Joachim Kremerskothen, Enhua Wang
The scaffolding protein WWC (WW and C2-domain containing) family is known to regulate cell proliferation and organ size via the Hippo signalling pathway. However, the expression level of WWC3 in human tumours and the mechanisms underlying its role in cellular signal transduction have not yet been reported. Herein, we explored the potential roles of WWC3 in lung cancer cells and the corresponding molecular mechanisms. We found low WWC3 expression in both lung cancer cell lines and lung cancer specimens, which was associated with low differentiation, advanced p-TNM stage, positive lymph node metastasis, and poor prognosis in patients with lung cancer...
May 25, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28523267/a-novel-role-for-the-bmp-antagonist-noggin-in-sensitizing-cells-to-non-canonical-wnt-5a-ror2-disheveled-pathway-activation
#8
Ondrej Bernatik, Tomasz Radaszkiewicz, Martin Behal, Zankruti Dave, Florian Witte, Annika Mahl, Nicole H Cernohorsky, Pavel Krejci, Sigmar Stricker, Vitezslav Bryja
Mammalian limb development is driven by the integrative input from several signaling pathways; a failure to receive or a misinterpretation of these signals results in skeletal defects. The brachydactylies, a group of overlapping inherited human hand malformation syndromes, are mainly caused by mutations in BMP signaling pathway components. Two closely related forms, Brachydactyly type B2 (BDB2) and BDB1 are caused by mutations in the BMP antagonist Noggin (NOG) and the atypical receptor tyrosine kinase ROR2 that acts as a receptor in the non-canonical Wnt pathway...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28513833/potential-role-and-prognostic-importance-of-dishevelled-2-in-epithelial-ovarian-cancer
#9
Rong Liu, Jialin Cheng, Yannan Chen, Wei Wang, Jie Chen, Guoxin Mao
OBJECTIVE: To investigate the role and prognostic importance of Dvl2 in human epithelial ovarian cancer (EOC). METHODS: A multimethod study was undertaken including patients with pathologically confirmed non-metastatic EOC who underwent surgery for maximum tumor resection at a center in China. Dvl2 expression was assessed by western blot using fresh EOC tissues and normal ovarian tissues obtained between June 2014 and January 2015. Additionally, retrospective data were obtained for patients treated between April 2004 and September 2009...
May 17, 2017: International Journal of Gynaecology and Obstetrics
https://www.readbyqxmd.com/read/28506997/the-phosphatase-pgam5-antagonizes-wnt-%C3%AE-catenin-signaling-in-embryonic-anterior-posterior-axis-patterning
#10
Verena Rauschenberger, Dominic B Bernkopf, Sabrina Krenn, Kowcee Jalal, Jens Heller, Jürgen Behrens, Marc Gentzel, Alexandra Schambony
The scaffold protein Dishevelled is a central intracellular component of Wnt signaling pathways. Various kinases have been described that regulate and modulate Wnt signaling through phosphorylation of Dishevelled. However, besides general protein phosphatases 1 and 2 (PP1 and PP2), no specific protein phosphatases have been identified. Here, we report on the identification and functional characterization of the protein phosphatase Pgam5 in vitro and in vivo in Xenopus Pgam5 is a novel antagonist of Wnt/β-Catenin signaling in human cells and Xenopus embryogenesis...
June 15, 2017: Development
https://www.readbyqxmd.com/read/28481871/suppression-of-planar-cell-polarity-signaling-and-migration-in-glioblastoma-by-nrdp1-mediated-dvl-polyubiquitination
#11
J H Wald, J Hatakeyama, I Printsev, A Cuevas, W H D Fry, M J Saldana, K VanderVorst, A Rowson-Hodel, J M Angelastro, C Sweeney, K L Carraway Rd
The lethality of the aggressive brain tumor glioblastoma multiforme (GBM) results in part from its strong propensity to invade surrounding normal brain tissue. Although oncogenic drivers such as epidermal growth factor receptor activation and Phosphatase and Tensin homolog inactivation are thought to promote the motility and invasiveness of GBM cells via phosphatidylinostitol 3-kinase activation, other unexplored mechanisms may also contribute to malignancy. Here we demonstrate that several components of the planar cell polarity (PCP) arm of non-canonical Wnt signaling including VANGL1, VANGL2 and FZD7 are transcriptionally upregulated in glioma and correlate with poorer patient outcome...
May 8, 2017: Oncogene
https://www.readbyqxmd.com/read/28463110/the-sec14-like-phosphatidylinositol-transfer-proteins-sec14l3-sec14l2-act-as-gtpase-proteins-to-mediate-wnt-ca-2-signaling
#12
Bo Gong, Weimin Shen, Wanghua Xiao, Yaping Meng, Anming Meng, Shunji Jia
The non-canonical Wnt/Ca(2+) signaling pathway plays important roles in embryonic development, tissue formation and diseases. However, it is unclear how the Wnt ligand-stimulated, G protein-coupled receptor Frizzled activates phospholipases for calcium release. Here, we report that the zebrafish/human phosphatidylinositol transfer protein Sec14l3/SEC14L2 act as GTPase proteins to transduce Wnt signals from Frizzled to phospholipase C (PLC). Depletion of sec14l3 attenuates Wnt/Ca(2+) responsive activity and causes convergent and extension (CE) defects in zebrafish embryos...
May 2, 2017: ELife
https://www.readbyqxmd.com/read/28455968/dishevelled-3-phosphorylation-is-governed-by-hipk2-pp1c%C3%AE-itch-axis-and-the-non-phosphorylated-form-promotes-cancer-stemness-via-lgr5-in-hepatocellular-carcinoma
#13
Yu-Man Tsui, Karen Man-Fong Sze, Edmund Kwok-Kwan Tung, Daniel Wai-Hung Ho, Terence Kin-Wah Lee, Irene Oi-Lin Ng
Dishevelled-3 (Dvl3) is regarded as a binding hub with many different interacting partners. However, its regulation and mechanism on cancer stemness remain to be explored. In this study, we showed that Dvl3 was significantly overexpressed in human hepatocellular carcinomas (HCCs) and promoted cancer stemness both in vitro and in vivo. We found that the non-phosphorylated (NP)-Dvl3 was more stable than the phosphorylated form, more active in activating β-catenin transcriptional activity, and more potent in enhancing self-renewal ability in HCC cells...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28447744/cyclic-compression-stimulates-osteoblast-differentiation-via-activation-of-the-wnt-%C3%AE-catenin-signaling-pathway
#14
Xi Chen, Jianmin Guo, Yu Yuan, Zhongguang Sun, Binglin Chen, Xiaoyang Tong, Lingli Zhang, Chao Shen, Jun Zou
It is widely accepted that mechanical stress is an important factor in bone associated cell differentiation, including that of mesenchymal stem cells, osteoblasts and osteocytes. The present study aimed to determine the effect of mechanical cyclic compressive load on osteoblast differentiation, and whether this was associated with activation of the wingless‑type (Wnt)/β-catenin signaling pathway. Using a 3D scaffold model, MC3T3‑E1 cells were exposed to cyclic compressive loading via the Flexcell‑5000C™ Compression system...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28418856/low-density-lipoprotein-receptor-related-protein-6-is-a-novel-coreceptor-of-protease-activated-receptor-2-in-the-dynamics-of-cancer-associated-%C3%AE-catenin-stabilization
#15
Jeetendra Kumar Nag, Arun Kancharla, Myriam Maoz, Hagit Turm, Daniel Agranovich, Chhedi Lal Gupta, Beatrice Uziely, Rachel Bar-Shavit
Protease-activated receptor-2 (PAR2) plays a central role in cancer; however, the molecular machinery of PAR2-instigated tumors remains to be elucidated. We show that PAR2 is a potent inducer of β-catenin stabilization, a core process in cancer biology, leading to its transcriptional activity. Novel association of low-density lipoprotein-related protein 6 (LRP6), a known coreceptor of Frizzleds (Fz), with PAR2 takes place following PAR2 activation. The association between PAR2 and LRP6 was demonstrated employing co-immunoprecipitation, bioluminescence resonance energy transfer (BRET), and confocal microscopy analysis...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28406046/depdc5-as-a-potential-therapeutic-target-for-epilepsy
#16
REVIEW
Kenneth A Myers, Ingrid E Scheffer
Dishevelled, Egl-10 and Pleckstrin (DEP) domain-containing protein 5 (DEPDC5) is a protein subunit of the GTPase-activating proteins towards Rags 1 (GATOR1) complex. GATOR1 is a recently identified modulator of mechanistic target of rapamycin (mTOR) activity. mTOR is a key regulator of cell proliferation and metabolism; disruption of the mTOR pathway is implicated in focal epilepsy, both acquired and genetic. Tuberous sclerosis is the prototypic mTOR genetic syndrome with epilepsy, however GATOR1 gene mutations have recently been shown to cause lesional and non-lesional focal epilepsy...
June 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28366812/dishevelled-stability-is-positively-regulated-by-pkc%C3%AE-mediated-phosphorylation-induced-by-wnt-agonists
#17
Dora M Velázquez, M Cristina Castañeda-Patlán, Martha Robles-Flores
Dishevelled (Dvl) proteins are central mediators of both canonical and non-canonical Wnt signaling. It is well known that, upon Wnt stimulation, Dvl becomes phosphorylated. However, how Wnt-induced phosphorylation of Dvl is regulated and its consequences are poorly understood. Here we found that Dvl proteins are overexpressed in colon cancer cells. In addition, we found that Wnt3a treatment rapidly induces hyperphosphorylation and stabilization of Dvl2 and Dvl3. The latter can be blocked by inhibition of Protein Kinase C (PKC)α, PKCδ, and PKCζ isoforms...
March 31, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28334810/bimodal-regulation-of-dishevelled-function-by-vangl2-during-morphogenesis
#18
Hwa-Seon Seo, Raymond Habas, Chenbei Chang, Jianbo Wang
Convergent extension (CE) is a fundamental morphogenetic mechanism that underlies numerous processes in vertebrate development, and its disruption can lead to human congenital disorders such as neural tube closure defects. The dynamic, oriented cell intercalation during CE is regulated by a group of core proteins identified originally in flies to coordinate epithelial planar cell polarity (PCP). The existing model explains how core PCP proteins, including Van Gogh (Vang) and Dishevelled (Dvl), segregate into distinct complexes on opposing cell cortex to coordinate polarity among static epithelial cells...
June 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28289771/coherent-array-of-branched-filamentary-scales-along-the-wing-margin-of-a-small-moth
#19
Akihiro Yoshida, Shin Tejima, Masayuki Sakuma, Yositaka Sakamaki, Ryuji Kodama
In butterflies and moths, the wing margins are fringed with specialized scales that are typically longer than common scales. In the hindwings of some small moths, the posterior margins are fringed with particularly long filamentary scales. Despite the small size of these moth wings, these scales are much longer than those of large moths and butterflies. In the current study, photography of the tethered flight of a small moth, Phthorimaea operculella, revealed a wide array composed of a large number of long filamentary scales...
April 2017: Die Naturwissenschaften
https://www.readbyqxmd.com/read/28288669/implication-of-overexpression-of-dishevelled-associated-activator-of-morphogenesis-1-daam-1-for-the-pathogenesis-of-human-idiopathic-pulmonary-arterial-hypertension-ipah
#20
Shun Yanai, Megumi Wakayama, Haruo Nakayama, Minoru Shinozaki, Hisayuki Tsukuma, Naobumi Tochigi, Tetsuo Nemoto, Tsutomu Saji, Kazutoshi Shibuya
BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is a rare, fatal disease of unknown pathogenesis. Evidence from our recent study suggests that IPAH pathogenesis is related to upregulation of the Wnt/planar cell polarity (Wnt/PCP) pathway. We used microscopic observation and immunohistochemical techniques to identify expression patterns of cascading proteins-namely Wnt-11, dishevelled-2 (Dvl-2), and dishevelled-associated activator of morphogenesis 1 (Daam-1)-in pulmonary arteries...
March 14, 2017: Diagnostic Pathology
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