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P-M Martin, R E Stanley, A P Ross, A E Freitas, C E Moyer, A C Brumback, J Iafrati, K S Stapornwongkul, S Dominguez, S Kivimäe, K A Mulligan, M Pirooznia, W R McCombie, J B Potash, P P Zandi, S M Purcell, S J Sanders, Y Zuo, V S Sohal, B N R Cheyette
Mice lacking DIX domain containing-1 (DIXDC1), an intracellular Wnt/β-catenin signal pathway protein, have abnormal measures of anxiety, depression and social behavior. Pyramidal neurons in these animals' brains have reduced dendritic spines and glutamatergic synapses. Treatment with lithium or a glycogen synthase kinase-3 (GSK3) inhibitor corrects behavioral and neurodevelopmental phenotypes in these animals. Analysis of DIXDC1 in over 9000 cases of autism, bipolar disorder and schizophrenia reveals higher rates of rare inherited sequence-disrupting single-nucleotide variants (SNVs) in these individuals compared with psychiatrically unaffected controls...
October 18, 2016: Molecular Psychiatry
Yu Ouyang, Fei Zhong, Qiru Wang, Linlin Ding, Peipei Zhang, Lingling Chen, Yuchan Wang, Chun Cheng
DIX domain containing 1 (DIXDC1), is a human homolog of Ccd1, a DIX domain containing protein in zebrafish. The present study was undertaken to determine the expression and biologic function of DIXDC1 in Non-Hodgkin's lymphoma (NHL). Clinically, we detected that the expression of DIXDC1 was significantly lower in the indolent lymphomas compared with the progressive lymphomas by immunohistochemistry analysis. Functionally, we found that DIXDC1 could promote cell proliferation via modulating cell cycle progression and PI3K/AKT signaling pathway in NHLs...
September 8, 2016: Leukemia Research
Weijie Wu, Qingqing Liu, Yuxi Liu, Zhaohui Yu, Youhua Wang
Dixdc1 (DIX domain containing-1), the mammalian homolog of Ccd1 (Coiled-coil-Dishevelled-Axin1), is a protein containing a coiled-coil domain and a Dishevelled-Axin (DIX) domain. As a novel component of the Wnt pathway, Dixdc1 has been reported to be able to promote neural progenitor proliferation and neuronal differentiation via Wnt/β-catenin signaling. But there still remains something unknown about Dixdc1 distribution and functions in the lesion and regeneration of the peripheral nervous system (PNS), so we tried to investigate dynamic changes of Dixdc1 expression in a rat sciatic nerve crush (SNC) model in this study...
September 16, 2016: Biochemical and Biophysical Research Communications
Xiaohong Li, Ying Xiao, Shaoqing Fan, Mingbing Xiao, Xiaotong Wang, Xiaolin Zhu, Xudong Chen, Chunsun Li, Guijuan Zong, Guoxiong Zhou, Chunhua Wan
DIX domain containing 1 (DIXDC1), a protein containing a coiled-coil domain and a Dishevelled-Axin (DIX) domain, is involved in the progression of multiple cancers. However, the role of DIXDC1 in human pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this study, we investigated the role and prognostic value of DIXDC1 in the development of human PDAC. Western blot analysis revealed that DIXDC1 was highly expressed in PDAC tissues and cell lines. Immunohistochemistry on 165 paraffin-embedded sections showed that high expression of DIXDC1 was significantly correlated with tumor size (P=...
August 3, 2016: Human Pathology
Senjun Zhou, Jiliang Shen, Shuang Lin, Xiaolong Liu, Ming Xu, Liang Shi, Xianfa Wang, Xiujun Cai
Dishevelled-Axin domain containing 1 (DIXDC1) is a DIX (Dishevelled-Axin) domain possessing protein that acts as a positive regulator of the Wnt pathway. Although DIXDC1 has been investigated in several cancers, it has not yet been studied in human hepatocellular carcinoma (HCC). The purpose of the current study was to investigate the expression pattern of DIXDC1 and assess the clinical significance of DIXDC1 expression in HCC patients. Data containing three independent investigations from Oncomine database demonstrated that DIXDC1 mRNA was downregulated in HCC compared with matched non-cancerous tissues...
July 28, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Kavita Shah, Debomoy K Lahiri
Cdk5, a cyclin-dependent kinase family member, is a global orchestrator of neuronal cytoskeletal dynamics. During embryogenesis, Cdk5 is indispensable for brain development. In adults, it is essential for numerous neuronal processes, including higher cognitive functions such as learning and memory formation, drug addiction, pain signaling, and long-term behavior changes through long-term potentiation and long-term depression, all of which rely on rapid alterations in the cytoskeleton. Cdk5 activity becomes deregulated in various brain disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, attention-deficit hyperactivity disorder, epilepsy, schizophrenia, and ischemic stroke; these all result in profound remodeling of the neuronal cytoskeleton...
March 5, 2016: Molecular Neurobiology
Lei Wang, Cong Tan, Fan Qiao, Weige Wang, Xiangnan Jiang, Peng Lian, Bin Chang, Weiqi Sheng
BACKGROUND: DIXDC1 (Dishevelled-Axin domain containing 1) is a positive regulator of the Wnt pathway. In the field of cancer research, the role of DIXDC1 is unclear. Our previous in vitro study showed that DIXDC1 enhances β-catenin nuclear accumulation in gastric cancer cell lines. The aim of this study was to detect the expression of DIXDC1 in different histological subtypes of gastric carcinoma and to evaluate the correlation between the expression of DIXDC1 and β-catenin localization and clinicopathological parameters, including patients' survival...
2015: Cancer Cell International
Cong Tan, Fan Qiao, Ping Wei, Yayun Chi, Weige Wang, Shujuan Ni, Qifeng Wang, Tongzhen Chen, Weiqi Sheng, Xiang Du, Lei Wang
DIXDC1 (Dishevelled-Axin domain containing 1) is a DIX (Dishevelled-Axin) domain-possessing protein that promotes colon cancer cell proliferation and increases the invasion and migration ability of non-small-cell lung cancer via the PI3K pathway. As a positive regulator of the Wnt/β-catenin pathway, the biological role of DIXDC1 in human gastric cancer and the relationship between DIXDC1 and the Wnt pathway are unclear. In the current study, the upregulation of DIXDC1 was detected in gastric cancer and was associated with advanced TNM stage cancer, lymph node metastasis, and poor prognosis...
April 2016: Molecular Carcinogenesis
Jonathan M Goodwin, Robert U Svensson, Hua Jane Lou, Monte M Winslow, Benjamin E Turk, Reuben J Shaw
The serine/threonine kinase LKB1 is a tumor suppressor whose loss is associated with increased metastatic potential. In an effort to define biochemical signatures of metastasis associated with LKB1 loss, we discovered that the epithelial-to-mesenchymal transition transcription factor Snail1 was uniquely upregulated upon LKB1 deficiency across cell types. The ability of LKB1 to suppress Snail1 levels was independent of AMPK but required the related kinases MARK1 and MARK4. In a screen for substrates of these kinases involved in Snail regulation, we identified the scaffolding protein DIXDC1...
August 7, 2014: Molecular Cell
Zhonghai Xu, Di Liu, Chuifeng Fan, Lan Luan, Xiupeng Zhang, Enhua Wang
DIX domain containing 1 (DIXDC1), is a human homolog of Ccd1, a recently identified DIX domain containing protein in zebrafish. DIXDC1 protein was detected in human colorectal adenocarcinoma tissues and was found to be correlated with a high cell proliferation index. We demonstrated DIXDC1 overexpression in 55% (92/167) of non-small cell lung cancer (NSCLC) cases, compared to adjacent noncancerous lung tissues (P < 0.01). Overexpression of DIXDC1 was associated with lymph node metastasis and more advanced TNM stage (P < 0...
November 2014: Molecular Carcinogenesis
Xiaohui Yan, Tianjiao Lyu, Nan Jia, Yinhua Yu, Keqin Hua, Weiwei Feng
Traditional Chinese medicine has gained popularity due to its ability to kill tumor cells. Recently, the apoptotic and anti-angiogenic effects of Trametes robiniophila murr (Huaier) have been investigated. The aim of this study was to investigate its effect on cell mobility and tumor growth in ovarian cancer. Cell viability and motility were measured using SRB, scratch and migration assays. Cell apoptosis was analysed by annexin V/PI staining. Using a reverse-phase protein array (RPPA) assay, we analyzed the levels of 153 proteins and/or phosphorylations in Huaier-treated and untreated cells...
2013: PloS One
Keita Uchino, Fumitaka Takeshita, Ryou-U Takahashi, Nobuyoshi Kosaka, Kae Fujiwara, Haruna Naruoka, Satoru Sonoke, Junichi Yano, Hideo Sasaki, Shiari Nozawa, Miki Yoshiike, Kazuki Kitajima, Tatsuya Chikaraishi, Takahiro Ochiya
Many reports have indicated that the abnormal expression of microRNAs (miRNAs) is associated with the progression of disease and have identified miRNAs as attractive targets for therapeutic intervention. However, the bifunctional mechanisms of miRNA guide and passenger strands in RNA interference (RNAi) therapy have not yet been clarified. Here, we show that miRNA (miR)-582-5p and -3p, which are strongly decreased in high-grade bladder cancer clinical samples, regulate tumor progression in vitro and in vivo...
March 2013: Molecular Therapy: the Journal of the American Society of Gene Therapy
S Kivimäe, P-M Martin, D Kapfhamer, Y Ruan, U Heberlein, J L R Rubenstein, B N R Cheyette
Disrupted-in-Schizophrenia-1 (DISC1) is a genetic susceptibility locus for major mental illness, including schizophrenia and depression. The Disc1 protein was recently shown to interact with the Wnt signaling protein, DIX domain containing 1 (Dixdc1). Both proteins participate in neural progenitor proliferation dependent on Wnt signaling, and in neural migration independently of Wnt signaling. Interestingly, their effect on neural progenitor proliferation is additive. By analogy to Disc1, mutations in Dixdc1 may lead to abnormal behavior in mice, and to schizophrenia or depression in humans...
2011: Translational Psychiatry
Cecilia Lai, James Robinson, Sue Clark, Gordon Stamp, Richard Poulsom, Andrew Silver
Peutz-Jeghers syndrome (PJS) is a rare, inherited disease caused by germline mutation of the LKB1 gene. Patients with PJS develop characteristic polyps in the digestive tract and carry an elevated risk of cancers in multiple organs, including the intestinal tract. While LKB1 is capable of phosphorylating AMPK and regulates the mTOR pathway, it is also known to be a multitasking protein that can influence other cellular processes, including cell polarity. We hypothesized that there may be other biological pathways directly or indirectly affected by the loss of LKB1 in PJS and aimed to investigate this possibility through transcriptional profiling of polyps harvested from an Lkb1(+/-) mouse model of PJS and from PJS patients...
April 2011: Journal of Pathology
Nicholas J Bradshaw, David J Porteous
In the decade since Disrupted in Schizophrenia 1 (DISC1) was first identified it has become one of the most convincing risk genes for major mental illness. As a multi-functional scaffold protein, DISC1 has multiple identified protein interaction partners that highlight pathologically relevant molecular pathways with potential for pharmaceutical intervention. Amongst these are proteins involved in neuronal migration (e.g. APP, Dixdc1, LIS1, NDE1, NDEL1), neural progenitor proliferation (GSK3β), neurosignalling (Girdin, GSK3β, PDE4) and synaptic function (Kal7, TNIK)...
March 2012: Neuropharmacology
Takashi Namba, Kozo Kaibuchi
The schizophrenia-associated protein DISC1 regulates several steps in neurogenesis. In a recent study published in Neuron, Singh et al. showed how DISC1 and its interacting partner Dixdc1 regulate cell proliferation and cell migration in different manners during embryonic neurogenesis.
July 20, 2010: Developmental Cell
Karun K Singh, Xuecai Ge, Yingwei Mao, Laurel Drane, Konstantinos Meletis, Benjamin A Samuels, Li-Huei Tsai
The psychiatric illness risk gene Disrupted in Schizophrenia-1 (DISC1) plays an important role in brain development; however, it is unclear how DISC1 is regulated during cortical development. Here, we report that DISC1 is regulated during embryonic neural progenitor proliferation and neuronal migration through an interaction with DIX domain containing-1 (Dixdc1), the third mammalian gene discovered to contain a Disheveled-Axin (DIX) domain. We determined that Dixdc1 functionally interacts with DISC1 to regulate neural progenitor proliferation by co-modulating Wnt-GSK3beta/beta-catenin signaling...
July 15, 2010: Neuron
Lei Wang, Hua Li, Qi Chen, Tengfang Zhu, Hongguang Zhu, Li Zheng
Wnt signaling plays key roles in development, cell growth, differentiation, polarity formation, neural development, and carcinogenesis. DIX Domain Containing 1 (DIXDC1), a novel component of the Wnt pathway, was recently cloned. DIXDC1 is the human homolog of Ccd1, a positive regulator of the Wnt signaling pathway during zebrafish neural patterning. Little has been known about DIXDC1 gene expression regulation. In the present study, we showed that the DIXDC1 protein was induced upon Wnt-3a stimulation, whereas the DIXDC1 mRNA level was not significantly increased after Wnt-3a treatment...
March 2010: Cancer Science
Lei Wang, Xi-Xi Cao, Qi Chen, Teng-Fang Zhu, Hong-Guang Zhu, Li Zheng
DIXDC1 is the human homolog of Ccd1, a recently identified DIX domain containing protein in zebrafish. It is a positive regulator in the Wnt signaling pathway functioning downstream of Wnt and upstream of Axin. Since Wnt pathway activation is correlated with human colon cancer formation and progression, the biological role of DIXDC1 in human colon cancer was examined. In the current study, up-regulation of DIXDC1 protein was detected in human colorectal adenocarcinoma tissues and was found to be correlated well with high cell proliferation index...
October 2009: Cancer Science
Tantan Liu, Lei Wang, Qi Chen, Li Zheng, Hongguang Zhu
DIXDC1, a novel type of DIX domain-containing protein in zebrafish, is the human homolog of Ccd1. It upregulates the Wnt signaling pathway functioning downstream of Wnt and upstream of axin. Here we aimed to efficiently generate a monoclonal antibody against DIXDC1 protein, using it as a tool to study the role of DIXDC1 in colonic tumorigenesis. We transformed the plasmids of PGEX-DIXDC1-C and PGEX-DIXDC1-N separately into Escherichia coli BL21 (DE3) for expression, and then injected the purified GST-DIXDC1 fusion protein into Balb/c mice...
June 2009: Hybridoma
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