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Wnt/b-catenin signal

Sajjad Karim, Jaudah A Al-Maghrabi, Hasan M A Farsi, Ahmad J Al-Sayyad, Hans-Juergen Schulten, Abdelbaset Buhmeida, Zeenat Mirza, Alaa A Al-Boogmi, Fai T Ashgan, Manal M Shabaad, Hend F NourEldin, Khalid B M Al-Ghamdi, Adel Abuzenadah, Adeel G A Chaudhary, Mohammed H Al-Qahtani
BACKGROUND: Renal cell carcinoma (RCC) is a seventh ranked malignancy with poor prognosis. RCC is lethal at metastatic stage as it does not respond to conventional systemic treatments, and there is an urgent need to find out promising novel biomarkers for effective treatment. The goal of this study was to evaluate the biomarkers that can be potential therapeutic target and predict effective inhibitors to treat the metastatic stage of RCC. METHODS: We conducted transcriptomic profiling to identify differentially expressed genes associated with RCC...
September 30, 2016: BMC Cancer
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
Logan Horne, Frank R Avilucea, Huifeng Jin, Jared J Barrott, Kyllie Smith-Fry, Yanliang Wang, Bang H Hoang, Kevin B Jones
Previous reports document expression of low-density lipoprotein receptor-related protein 5 (LRP5) in osteosarcoma (OS) tissue. Expression of this Wnt receptor correlated with metastatic disease and poor disease-free survival. Forced expression of dominant-negative LRP5 (dnLRP5), which lacks the membrane binding domain of the native protein and therefore functions as a soluble receptor-sponge for Wnt ligands, reduced in vitro cellular invasion and in vivo xenograft tumor growth for osteosarcoma cell lines. Here, we use a genetically engineered mouse model of osteosarcomagenesis with and without expression of dnLRP5 to assess to what degree tumorigenesis is affected and whether Wnt/β-catenin signaling is circumvented or maintained...
October 2016: Translational Oncology
Zhuhong Zhang, Jing Yin, Jian Yang, Wenzhi Shen, Chunyan Zhang, Wenjun Mou, Jinhua Luo, Hua Yan, Peiqing Sun, Yunping Luo, Yaping Tian, Rong Xiang
MicroRNAs (miRNAs) inhibit or improve the malignant progression of hepatocellular carcinoma (HCC). We previously reported that compared to health controls, patients with liver cirrhosis present the highest levels of circulating miR-885-5p, followed by those with chronic hepatitis B and those with HCC. However, the molecular involvement of miR-885-5p in HCC metastasis is presently unclear. Here, we demonstrated that the expression of miR-885-5p negatively correlated with the invasive and metastatic capabilities of human HCC tissue samples and cell lines...
October 12, 2016: Oncotarget
Leen Bussche, Gat Rauner, Mark Antonyak, Bethany Syracuse, Melissa McDowell, Anthony M C Brown, Richard A Cerione, Gerlinde R Van de Walle
Signaling mechanisms that regulate mammary stem/progenitor cell (MaSC) self-renewal are essential for developmental changes that occur in the mammary gland during pregnancy, lactation and involution. We observed that equine MaSCs (eMaSCs) maintain their growth potential in culture for an indefinite period, while canine MaSCs (cMaSCs) lose their growth potential in long-term cultures. We then used this system to investigate the role of microvesicles (MVs) in promoting self-renewal properties. We found that Wnt3a and Wnt1 were expressed at higher levels in MVs isolated from eMaSCs compared to those from cMaSCs...
October 12, 2016: Journal of Biological Chemistry
Xia Yang, Jian-Ning Lv, Hui Li, Bo Jiao, Qiu-Hong Zhang, Yong Zhang, Jie Zhang, Yan-Qin Liu, Ming Zhang, Hu Shan, Jin-Zhao Zhang, Run-Miao Wu, Ya-Li Li
OBJECTIVES: Asthma is a chronic inflammatory, heterogeneous airway disease affecting millions of people around the world. Curcumin has been found to have anti-inflammatory and antifibrosis effects. Researchers reported that curcumin regulated Wnt/b-catenin signaling in lots of cells. However, whether curcumin regulates the levels of Wnt/ b-Catenin signaling in lung tissues and DCs (dendritic cells) remains unclear. In this study, we assessed the effects of curcumin on DCs and asthma. METHODS: C57BL/6 mice immunized with OVA (ovalbumin) were challenged thrice with an aerosol of OVA every second day for 8 days...
August 15, 2016: Journal of Asthma: Official Journal of the Association for the Care of Asthma
L Farahmand, B Darvishi, K Majidzadeh-A, A Madjid Ansari
Despite numerous remarkable achievements in the field of anti-cancer therapy, tumour relapse and metastasis still remain major obstacles in improvement of overall cancer survival, which may be at least partially owing to epithelial-mesenchymal transition (EMT). Multiple signalling pathways have been identified in EMT; however, it appears that the role of the Hedgehog and WNT/β-catenin pathways are more prominent than others. These are well-known preserved intracellular regulatory pathways of different cellular functions including proliferation, survival, adhesion and differentiation...
September 27, 2016: Cell Proliferation
Dongdong Han, Chengjie Cao, Ya Su, Jun Wang, Jian Sun, Huasheng Chen, Aihua Xu
ETHNOPHARMACOLOGICAL RELEVANCE: A fruit of Ginkgo biloba L. also known as Ginkgo biloba, can be used for the treatment of cancer in Chinese traditional medicine. The scientific name of succulent skin, which is the episperm of Ginkgo nuts, is exocarp. Experiment shows that Ginkgo biloba exocarp extracts (GBEE) has the effects of immune promotion, cancer inhibition and etc. AIM OF STUDY: Study on the activity of GBEE against Lewis lung cancer (LLC) angiogenesis and its partial molecular mechanism...
November 4, 2016: Journal of Ethnopharmacology
C-C Liu, D-L Cai, F Sun, Z-H Wu, B Yue, S-L Zhao, X-S Wu, M Zhang, X-W Zhu, Z-H Peng, D-W Yan
We previously demonstrated that fermitin family member 1 (FERMT1) was significantly overexpressed in colon cancer (CC) and associated with poor metastasis-free survival. This study aimed to investigate the precise role of FERMT1 in CC metastasis and the mechanism by which FERMT1 is involved in the epithelial-mesenchymal transition (EMT). Correlations between FERMT1 and EMT markers (E-cadherin, Slug, N-cadherin and β-catenin) were examined via immunohistochemistry in a cohort of CC tissues and adjacent normal colon mucosae...
September 19, 2016: Oncogene
Alireza Milani, Marzieh Basirnejad, Sepideh Shahbazi, Azam Bolhassani
Carotenoids and retinoids have several similarities in biological activities such as antioxidant properties, the inhibition of malignant tumor growth, and the induction of apoptosis. Supplementation with carotenoids can influence cell growth regulation, and modulate gene expression and immune response. Epidemiologic studies have shown the correlation of high carotenoid intake from food sources with reduced risk of breast, cervical, ovarian, colorectal cancers, and cardiovascular or eye diseases. Cancer chemoprevention by dietary carotenoids involves some approaches including gap junctional intercellular communication (GJIC), growth factor signaling, cell cycle progression, differentiation-related proteins, retinoid-like receptors, antioxidant response element, nuclear receptors, AP-1 transcriptional complex, Wnt/β-Catenin pathway, and inflammatory cytokines...
September 16, 2016: British Journal of Pharmacology
Aditya K Gupta, Jessie Carviel
BACKGROUND: Platelet-rich plasma (PRP) therapy is a novel procedure used to treat androgenetic alopecia (AGA). OBJECTIVE: Propose a mechanism of action of PRP therapy for AGA. METHODS AND MATERIALS: A thorough literature search including PRP research for AGA therapy as well as PRP research in other areas of medicine was conducted. RESULTS: A mechanistic model for the action of PRP on the hair follicle was created. CONCLUSION: Platelet-rich plasma therapy stimulates hair growth through the promotion of vascularization and angiogenesis, as well as encourages hair follicles to enter and extend the duration of the anagen phase of the growth cycle...
September 14, 2016: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
Angelo B A Laranjeira, Sherry X Yang
Cancer stem cells (CSCs), also known as tumor initialing cells, have self-renewal capacity and are believed to play an important role in residual disease or tumor relapse. CSCs exhibit characteristic slow growth rate and are resistant to conventional chemotherapy/radiotherapy in experimental models. The type of cells commonly employs aberrant activity of the embryonic signal transduction pathways - Notch, Hedgehog (Hh), and Wnt - for uncontrolled proliferation and survival. Areas covered: The following article discusses key genetic and molecular alterations in Notch, Hh and Wnt pathways and drugs targeting the alterations for the treatment of leukemia and lymphoma...
November 2016: Expert Opinion on Drug Discovery
Florence Morin, Niloufar Kavian, Carole Nicco, Olivier Cerles, Christiane Chéreau, Frédéric Batteux
Systemic sclerosis (SSc) is a connective tissue disorder characterized by fibrosis of the skin and inner organs, vasculopathy, and immunological abnormalities. Recent insights on the implication of STAT3, AKT, and Wnt/β-catenin in fibrosis have prompted us to investigate, in a mouse model of ROS-induced SSc, the effects of niclosamide, an antihelmintic drug that inhibits both of these signaling pathways. SSc was induced in BALB/c mice by daily s.c. injections of hypochlorous acid (HOCl). Mice were treated or not every other day, 5 d a week, for 6 wk, by niclosamide...
September 9, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Lingxiang Hu, Jingrong Lu, Hao Chiang, Hao Wu, Albert S B Edge, Fuxin Shi
UNLABELLED: Cochlear hair cells (HCs), the sensory cells that respond to sound, do not regenerate after damage in adult mammals, and their loss is a major cause of deafness. Here we show that HC regeneration in newborn mouse ears occurred spontaneously when the original cells were ablated by treatment with diphtheria toxin (DT) in ears that had been engineered to overexpress the DT receptor, but was not detectable when HCs were ablated in vivo by the aminoglycoside antibiotic neomycin...
September 7, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
X Yang, D Hao, H Zhang, B Liu, M Yang, B He
: Treatment with hydrogen sulfide mitigates spinal cord injury-induced sublesional bone loss, possibly through abating oxidative stress, suppressing MMP activity, and activating Wnt/β-catenin signaling. INTRODUCTION: Spinal cord injury (SCI)-induced sublesional bone loss represents the most severe osteoporosis and is resistant to available treatments to data. The present study was undertaken to explore the therapeutic potential of hydrogen sulfide (H2S) against osteoporosis in a rodent model of motor complete SCI...
September 3, 2016: Osteoporosis International
D A Maschio, R B Oliveira, M R Santos, C P F Carvalho, H C L Barbosa-Sampaio, C B Collares-Buzato
The Wnt/β-catenin signaling pathway, also known as the canonical Wnt pathway, plays a role in cell proliferation and differentiation in several tissues/organs. It has been recently described in humans a relationship between type 2 diabetes (T2DM) and mutation in the gene encoding the transcription factor TCF7L2 associated to the Wnt/β-catenin pathway. In the present study, we demonstrated that hyperplastic pancreatic islets from prediabetic mice fed a high-fat diet (HFD) for 60 d displayed nuclear translocation of active β-catenin associated with significant increases in protein content and gene expression of β-catenin as well as of cyclins D1, D2 and c-Myc (target genes of the Wnt pathway) but not of Tcf7l2 (the transcription factor)...
September 30, 2016: Biochemical and Biophysical Research Communications
Vivian Weiss, Julie Dueber, Jesse P Wright, Justin Cates, Frank Revetta, Alexander A Parikh, Nipun B Merchant, Chanjuan Shi
AIM: To investigate the role of the Wnt/β-catenin pathway in pancreatic neuroendocrine neoplasms (PanNENs). METHODS: Tissue microarrays containing 88 PanNENs were immunohistochemically labeled with antibodies to β-catenin, E-cadherin, adenomatous polyposis coli (APC), chromogranin and synaptophysin. One case had only metastatic tumors resected, whereas others (n = 87) received pancreatectomy with or without partial hepatectomy. Pathology slides, demographic, clinicopathologic, and follow up data were reviewed...
August 15, 2016: World Journal of Gastrointestinal Oncology
Nahal R Lalefar, Andrzej Witkowski, Jens B Simonsen, Robert O Ryan
BACKGROUND: Wnt proteins modulate development, stem cell fate and cancer through interactions with cell surface receptors. Wnts are cysteine-rich, glycosylated, lipid modified, two domain proteins that are prone to aggregation. The culprit responsible for this behavior is a covalently bound palmitoleoyl moiety in the N-terminal domain. RESULTS: By combining murine Wnt3a with phospholipid and apolipoprotein A-I, ternary complexes termed nanodisks (ND) were generated...
2016: Journal of Nanobiotechnology
Jacob J Orme, Yong Du, Kamala Vanarsa, Tianfu Wu, Anne B Satterthwaite, Chandra Mohan
Wnt/β-catenin signaling is relatively understudied in immunity and autoimmunity. β-catenin blocks inflammatory mediators and favors tolerogenic dendritic cell (DC) phenotypes. We show here that leukocytes from lupus-prone mice and SLE patients express diminished β-catenin transcriptional activity, particularly in myeloid cells, although other leukocytes revealed similar trends. Serum levels of DKK-1, an inhibitor under transcriptional control of Wnt/β-catenin, were also decreased in lupus-prone mice. Surprisingly, however, preemptive deletion of β-catenin from macrophages appears to have no effect on lupus development, even in mice with varying genetic loads for lupus...
2016: PloS One
Shou-Song Gao, Xiao-Hong Yang, Meng Wang
B-cell translocation gene 2 (BTG2), a tumor suppressor gene, is downregulated in several types of human cancer cell. However, its function in skin cancer cells has not been fully elucidated. Therefore, the present study investigated the expression and function of BTG2 in skin cancer cells, and investigated the underlying molecular mechanism. The results indicated that BTG2 expression was downregulated in skin cancer cell lines. Overexpression of BTG2 significantly inhibited cell proliferation, cell cycle progression, and the invasion and migration of skin cancer cells...
October 2016: Molecular Medicine Reports
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