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Xin Gao, Liao-Yuan Li, Jörg Rassler, Jun Pang, Ming-Kun Chen, Wei-Peng Liu, Zheng Chen, Shan-Cheng Ren, Fang-Jian Zhou, Ke-Ji Xie, Xing Zhou, Hui-Jun Qian, Xian-Zhong Bai, Jiu-Min Liu, Jiang-Gen Yang, Dan He, Chun-Kui Shao, Zu-Lan Su, Jing Wang, Jian-Guang Qiu, Li Ling
BACKGROUND: For patients with prostate cancer (PCa), the presence of pelvic lymph node metastasis (LNM) is a strong predictor of poor outcome. However, the approaches with promising sensitivity and specificity to detect LNM are still lacking. We investigated the value of collapsin response mediator protein 4 (CRMP4) promoter methylation in biopsies as a predictor for LNM. METHODS: CRMP4 promoter methylation at two previously identified CpG sites was determined in 80 case-matched biopsy samples (the training set) using bisulfite pyrosequencing...
January 2017: Journal of the National Cancer Institute
Basem M Abdallah, Florence Figeac, Kenneth H Larsen, Nicholas Ditzel, Pankaj Keshari, Adiba Isa, Abbas Jafari, Thomas L Andersen, Jean-Marie Delaisse, Yoshio Goshima, Toshio Ohshima, Moustapha Kassem
We identified the neuroprotein collapsing response mediator protein-4 (CRMP4) as a noncanonical osteogenic factor that regulates the differentiation of mouse bone marrow skeletal stem cells (bone marrow stromal stem cells [mBMSCs]) into osteoblastic cells. CRMP4 is the only member of the CRMP1-CRMP5 family to be expressed by mBMSCs and in osteoprogenitors of both adult mouse and human bones. In vitro gain-of-function and loss-of-function of CRMP4 in murine stromal cells revealed its inhibitory effect on osteoblast differentiation...
December 26, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Ryosuke Takaya, Jun Nagai, Wenfui Piao, Emi Niisato, Takeru Nakabayashi, Yuki Yamazaki, Fumio Nakamura, Naoya Yamashita, Papachan Kolattukudy, Yoshio Goshima, Toshio Ohshima
Neural circuit formation is a critical process in brain development. Axon guidance molecules, their receptors, and intracellular mediators are important to establish neural circuits. Collapsin response mediator proteins (CRMPs) are known intercellular mediators of a number of repulsive guidance molecules. Studies of mutant mice suggest roles of CRMPs in dendrite development. However, molecular mechanisms of CRMP-mediated dendritic development remain to elucidate. In this study, we show abnormal orientation of basal dendrites (extension to deeper side) of layer V pyramidal neurons in the cerebral cortex of CRMP4-/- mice...
January 15, 2017: Brain Research
Haijian Guo, Bing Xia
BACKGROUND: Collapsin response mediator proteins (CRMPs) were originally identified in the nervous system and are involved in neuronal development. Similar to CRMP1, CRMP4 has a shorter transcript encoding a short isoform known as CRMP4a, and a longer transcript encoding a long isoform known as CRMP4b. Previous studies have shown that CRMP4a and CRMP4b exhibit opposing functions in neurite outgrowth. In the present study, we aimed to determine whether CRMP4a and CRMP4b have divergent effects in gastric cancer...
2016: BMC Cancer
Caihui Cha, Jifeng Zhang, Zhisheng Ji, Minghui Tan, Sumei Li, Fengming Wu, Keen Chen, Sitang Gong, Guoqing Guo, Hongsheng Lin
CRMP family proteins (CRMPs) are critical for neurite outgrowth and maturation in the developing nervous system. However, the distinct roles of CRMP isoforms remain to be elucidated, especially in dendritic development. Here, we show that CRMP4 is sufficient and necessary for dendritic growth and maturation in cultured hippocampal neurons. Overexpression of CRMP4 promotes and genetic knockdown of CRMP4 inhibits the amount of dendritic tips, total dendritic length, spine density, and the frequency but not amplitude of miniature excitatory synaptic current...
June 2016: Brain Research Bulletin
Sho Sato, Fumio Nakamura, Yukihiko Hiroshima, Yoji Nagashima, Ikuma Kato, Naoya Yamashita, Yoshio Goshima, Itaru Endo
BACKGROUND: Chronic pancreatitis is a significant risk factor for pancreatic cancer. Previously, we demonstrated that the pancreatic cancer cells show enhanced expression of collapsin response mediator protein 4 (CRMP4) that strongly correlates with severe venous invasion, liver metastasis, and poor prognosis. However, involvement of CRMP4 in acute or chronic pancreatitis remains unknown. METHODS: Acute and chronic pancreatitis mice models were developed by periodic injection of caerulein...
July 2016: Journal of Hepato-biliary-pancreatic Sciences
Changlin Li, Wencong Jiang, Qingting Hu, Long-Cheng Li, Liang Dong, Ruibao Chen, Yinghong Zhang, Yuzhe Tang, J Brantley Thrasher, Chang-Bai Liu, Benyi Li
To explore a novel strategy in suppressing tumor metastasis, we took the advantage of a recent RNA activation (RNAa) theory and used small double-strand RNA molecules, termed as small activating RNAs (saRNA) that are complimentary to target gene promoter, to enhance transcription of metastasis suppressor gene. The target gene in this study is Dihydro-pyrimidinase-like 3 (DPYSL3, protein name CRMP4), which was identified as a metastatic suppressor in prostate cancers. There are two transcriptional variants of DPYSL3 gene in human genome, of which the variant 2 is the dominant transcript (DPYSL3v2, CRMP4a) but is also significantly down-regulated in primary prostate cancers...
April 19, 2016: Oncotarget
Jun Nagai, Ryosuke Takaya, Wenhui Piao, Yoshio Goshima, Toshio Ohshima
The capacity for regeneration in the injured adult mammalian central nervous system (CNS) is largely limited by potent inhibitory barriers. Chondroitin sulfate proteoglycans (CSPGs) are major inhibitors of axonal regeneration/sprouting and accumulate at lesion sites after CNS trauma. Despite extensive research during the two decades since their discovery, the molecular mechanisms remain elusive, including intracellular phosphorylation events. Collapsin response mediator protein 4 (CRMP4) is known to directly regulate cytoskeletal dynamics and neurite extension, while phosphorylated CRMP4 loses its binding affinity for cytoskeletal proteins...
July 2016: Molecular and Cellular Neurosciences
Aine Tonouchi, Jun Nagai, Kentaro Togashi, Yoshio Goshima, Toshio Ohshima
Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by the selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Several lines of evidence suggest that neurodegeneration in PD is accelerated by a vicious cycle in which apoptosis in dopaminergic neurons triggers the activation of microglia and harmful inflammatory processes that further amplify neuronal death. Recently, we demonstrated that the deletion of collapsin response mediator protein 4 (CRMP4) suppresses inflammatory responses and cell death in a mouse model of spinal cord injury, leading to improved functional recovery...
June 2016: Journal of Neurochemistry
Sile Chen, Xinhua Zhang, Jianjun Peng, Ertao Zhai, Yulong He, Hui Wu, Chuangqi Chen, Jinping Ma, Zhao Wang, Shirong Cai
This study aimed to investigate the precise role of CRMP4 in gastric tumor growth and patient survival. The mRNA and protein expression levels of CRMP4, VEGF and VEGFR2 were validated by qRT-PCR and immunohistochemistry. We investigated the effects on tumor growth of overexpression and knockdown of CRMP4 both in vitro and in vivo by constructing stable gastric cell lines using lentiviral-mediated transduction and shRNA interference-mediated knockdown of CRMP4 expression. We further validated the role of the ERK/AKT signaling pathways in VEGF and CRMP4 expression using ERK and PI3K inhibitors...
March 29, 2016: Oncotarget
Atsuhiro Tsutiya, Hikaru Watanabe, Yui Nakano, Masugi Nishihara, Yoshio Goshima, Ritsuko Ohtani-Kaneko
Collapsin response mediator protein 4 (CRMP4), a member of the CRMP family, is involved in the pathogenesis of neurodevelopmental disorders such as schizophrenia and autism. Here, we first compared layer thickness of the olfactory bulb between wild-type (WT) and CRMP4-knockout (KO) mice. The mitral cell layer (MCL) was significantly thinner, whereas the external plexiform layer (EPL) was significantly thicker in CRMP4-KO mice at postnatal day 0 (PD0) compared with WTs. However, differences in layer thickness disappeared by PD14...
May 2016: Journal of Anatomy
Atsuhiro Tsutiya, Masugi Nishihara, Yoshio Goshima, Ritsuko Ohtani-Kaneko
Members of the collapsin response mediator protein (CRMP) family are reported to be involved in the pathogenesis of various neuronal disorders, including schizophrenia and autism. One of them, CRMP4, is reported to participate in aspects of neuronal development, such as axonal guidance and dendritic development. However, no physiological or behavioral phenotypes in Crmp4 knockout (Crmp4-KO) mice have been identified, making it difficult to elucidate the in vivo roles of CRMP4. Focusing on the olfaction process because of the previous study showing strong expression of Crmp4 mRNA in the olfactory bulb (OB) during the early postnatal period, it was aimed to test the hypothesis that Crmp4-KO pups would exhibit abnormal olfaction...
September 2015: European Journal of Neuroscience
Minghui Tan, Caihui Cha, Yongheng Ye, Jifeng Zhang, Sumei Li, Fengming Wu, Sitang Gong, Guoqing Guo
Cytoskeleton dynamics are critical phenomena that underpin many fundamental cellular processes. Collapsin response mediator proteins (CRMPs) are highly expressed in the developing nervous system, mediating growth cone guidance, neuronal polarity, and axonal elongation. However, whether and how CRMPs associate with microtubules and actin coordinated cytoskeletal dynamics remain unknown. In this study, we demonstrated that CRMP2 and CRMP4 interacted with tubulin and actin in vitro and colocalized with the cytoskeleton in the transition-zone in developing growth cones...
2015: Neural Plasticity
Ke Li, Jun Pang, Huaiyan Cheng, Wei-Peng Liu, Jin-Ming Di, Heng-Jun Xiao, Yun Luo, Hao Zhang, Wen-Tao Huang, Ming-Kun Chen, Liao-Yuan Li, Chun-Kui Shao, Ying-Hong Feng, Xin Gao
Prostate cancer is the most commonly diagnosed non-cutaneous cancer and one of the leading causes of cancer death for North American men. Whereas localized prostate cancer can be cured, there is currently no cure for metastatic prostate cancer. Here we report a novel approach that utilizes designed chimeric transcription activator-like effectors (dTALEs) to control prostate cancer metastasis. Transfection of dTALEs of DNA methyltransferase or demethylase induced artificial, yet active locus-specific CpG and subsequent histone modifications...
April 30, 2015: Oncotarget
Jun Nagai, Yoshiteru Kitamura, Kazuki Owada, Naoya Yamashita, Kohtaro Takei, Yoshio Goshima, Toshio Ohshima
Axonal outgrowth inhibitors and scar formation are two major obstacles to central nervous system (CNS) repair. No target molecule that regulates both axonal growth and scarring has been identified. Here we identified collapsin response mediator protein 4 (CRMP4), a common mediator of inhibitory signals after neural injury, as a crucial factor that contributes to both axonal growth inhibition and scarring after spinal cord injury (SCI). We found increases in the inhibitory and toxic forms of CRMP4 in injured spinal cord...
2015: Scientific Reports
Sylwia Kedracka-Krok, Bianka Swiderska, Urszula Jankowska, Bozena Skupien-Rabian, Joanna Solich, Katarzyna Buczak, Marta Dziedzicka-Wasylewska
For over the last 50 years, the molecular mechanism of anti-psychotic drugs' action has been far from clear. While risperidone is very often used in clinical practice, the most efficient known anti-psychotic drug is clozapine (CLO). However, the biochemical background of CLO's action still remains elusive. In this study, we performed comparative proteomic analysis of rat cerebral cortex following chronic administration of these two drugs. We observed significant changes in the expression of cytoskeletal, synaptic, and regulatory proteins caused by both antipsychotics...
March 2015: Journal of Neurochemistry
Wei Zhou, Peigen Xie, Mao Pang, Bu Yang, Youqiang Fang, Tao Shu, Chang Liu, Xuan Wang, Liangming Zhang, Shangfu Li, Limin Rong
Prostate cancer, the most commonly diagnosed male cancer in North America, has a high incidence of bone metastasis. Our previous study showed collapsin response mediator protein 4 (CRMP4) gene inhibited prostate cancer migration and invasion. In this study, we investigated whether overexpression of CRMP4 gene in prostate cancer cells inhibit tumor bone metastasis. The stable prostate cancer cells overexpressing the CRMP4 gene were constructed using lentivirus infection. Prostate cancer bone metastasis nude mouse model was built though orthotopic prostate implantation, intracardiac injection and intratibial injection with CRMP4 overexpress and control cancer cells...
January 2015: International Journal of Oncology
Mohamad R Khazaei, Marie-Pier Girouard, Ricardo Alchini, Stephan Ong Tone, Tadayuki Shimada, Susanne Bechstedt, Mitra Cowan, Dominique Guillet, Paul W Wiseman, Gary Brouhard, Jean Francois Cloutier, Alyson E Fournier
Coordinated control of the growth cone cytoskeleton underlies axon extension and guidance. Members of the collapsin response mediator protein (CRMP) family of cytosolic phosphoproteins regulate the microtubule and actin cytoskeleton, but their roles in regulating growth cone dynamics remain largely unexplored. Here, we examine how CRMP4 regulates the growth cone cytoskeleton. Hippocampal neurons from CRMP4-/- mice exhibited a selective decrease in axon extension and reduced growth cone area, whereas overexpression of CRMP4 enhanced the formation and length of growth cone filopodia...
October 24, 2014: Journal of Biological Chemistry
Mohammad R Khazaei, Samuel Montcalm, Adriana Di Polo, Alyson E Fournier, Yves Durocher, Stephan Ong Tone
Neurons fail to re-extend their processes within the central nervous system environment in vivo, and this is partly because of inhibitory proteins expressed within myelin debris and reactive astrocytes that actively signal to the injured nerve cells to limit their growth. The ability of the trans-acting activator of transcription (TAT) protein transduction domain (PTD) to transport macromolecules across biological membranes raises the possibility of developing it as a therapeutic delivery tool for nerve regeneration...
February 2015: Journal of Molecular Neuroscience: MN
Daniela Nogueira Rocha, Pedro Brites, Carlos Fonseca, Ana Paula Pêgo
Mammalian central nervous system (CNS) neurons do not regenerate after injury due to the inhibitory environment formed by the glial scar, largely constituted by myelin debris. The use of biomaterials to bridge the lesion area and the creation of an environment favoring axonal regeneration is an appealing approach, currently under investigation. This work aimed at assessing the suitability of three candidate polymers - poly(ε-caprolactone), poly(trimethylene carbonate-co-ε-caprolactone) (P(TMC-CL)) (11∶89 mol%) and poly(trimethylene carbonate) - with the final goal of using these materials in the development of conduits to promote spinal cord regeneration...
2014: PloS One
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