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stem signaling pathway

Eleonora Orlando, Daniel Matthias Aebersold, Michaela Medová, Yitzhak Zimmer
Following nearly two decades of its conception, the phenomenon of oncogene addiction still represents a key concept of how progresses in basic research can translate to unprecedented translational breakthroughs. Coined by Bernard Weinstein, this term refers to the phenomenon by which cancer cells can exhibit dependence on a single oncogenic protein or signaling pathway for sustaining proliferation and survival, despite the wide burden of genetic lesions characterizing their genomic background, revealing thus a promising Achilles' heel of cancer...
December 11, 2018: Cancer Letters
Ping Li, Qi Deng, Jiajia Liu, Jianshe Yan, Zhanying Wei, Zhenlin Zhang, Huijuan Liu, Baojie Li
HB-EGF, a member of the EGF superfamily, plays important roles in development and tissue regeneration. However, its functions in skeletal stem cells and skeleton development and growth remain poorly understood. Here, we used the Cre/LoxP system to ablate or express HB-EGF in Dermo1+ mesenchymal stromal cells and their progenies, including chondrocytes and osteoblast lineage cells, and bone marrow stromal cells (BMSCs). Dermo1-Cre; HB-EGFf/f mice only showed a modest increase in bone mass, whereas Dermo1-HB-EGF mice developed progressive chondrodysplasia, chondroma, osteoarthritis-like joint defects, and loss of bone mass and density, which were alleviated by treatment with EGFR inhibitor AG1478...
December 14, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Shuyun Rao, Lopa Mishra
Hepatocellular carcinoma (HCC), accounting for 85-90% of all primary liver cancers, is among the most prevalent and lethal cancers in the world, with five-year survival for advanced cases under 11%. Ineffective detection of tumors and drug resistance are some of the causal factors for therapy failure. Thus, there is an urgent need to understand the molecular mechanisms underlying drug resistance and HCC initiation. Development of HCC is associated with alterations in the TGF-β signaling pathway which plays a critical role in cell proliferation, apoptosis, differentiation, motility, lineage specificity, as well as normal stem cell homeostasis...
December 14, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Ritu Khosla, Ashish Kumar Vyas, Nirupma Trehanpati
Notch signaling is an evolutionarily conserved multifaceted pathway that controls diverse cellular processes. Its role in regulating development and tissue homeostasis is well established. Aberrant activation of the Notch pathway has been implicated in the initiation and progression of many types of cancers. However, although in some cancers Notch signaling acts as a tumor-promoter, in others it is reported to suppress tumor growth and progression. Accumulating evidence suggests the involvement of both the innate and adaptive immune system in the development of various tumors...
December 13, 2018: Scandinavian Journal of Immunology
Somayeh Aslani, Alireza Abhari, Ebrahim Sakhinia, Davoud Sanajou, Hadi Rajabi, Sevda Rahimzadeh
Osteoblasts are terminally differentiated cells with mesenchymal origins, known to possess pivotal roles in sustaining bone microstructure and homeostasis. These cells are implicated in the pathophysiology of various bone disorders, especially osteoporosis. Over the last few decades, strategies to impede bone resorption, principally by bisphosphonates, have been mainstay of treatment of osteoporosis; however, in recent years more attention has been drawn on bone-forming approaches for managing osteoporosis...
December 12, 2018: Journal of Cellular Physiology
Ming Tan, Mohammad Asad, Valerie Heong, Meng Kang Wong, Tuan Zea Tan, Jieru Ye, Kuee Theng Kuay, Jean Paul Thiery, Clare Scott, Ruby Yun-Ju Huang
Frizzled family receptor 7 (FZD7), a Wnt signaling receptor, is associated with the maintenance of stem cell properties and cancer progression. FZD7 has emerged as a potential therapeutic target because it is capable of transducing both canonical and non-canonical Wnt signals. In this study, we investigated the regulatory pathway downstream of FZD7 and its functional roles. We found that FZD7 expression was crucial to the maintenance of the mesenchymal phenotype, anoikis resistance, and spheroid and tumour formation in ovarian cancer...
December 11, 2018: Molecular Oncology
Fatemeh Sharifpanah, Enas Hussein Ali, Maria Wartenberg, Heinrich Sauer
The milk thistle compound Silibinin (i.e., a 1:1 mixture of Silybin A and Silybin B) stimulates vasculogenesis of mouse embryonic stem (ES) cells. Because vasculogenesis and leukopoiesis are interrelated, the effect of Silibinin on leukopoiesis of ES cells was investigated. Treatment of differentiating ES cells with hydrosoluble Silibinin-C-2',3-dihydrogen succinate dose-dependent increased the number of CD18+ , CD45+ , and CD68+ cells, indicating leukocyte/macrophage differentiation. Silibinin treatment activated phosphoinositide 3-kinase (PI3K), AKT (protein kinase B), signal transducer and activator of transcription 3 (STAT3), stimulated hypoxia-induced factor-1α (HIF-1α), and vascular endothelial growth factor receptor 2 (VEGFR2) expression and raised intracellular nitric oxide (NO)...
December 11, 2018: Phytotherapy Research: PTR
Sreejit Parameswaran, Frederick S Vizeacoumar, Kalpana Kalyanasundaram Bhanumathy, Fujun Qin, Md Fahmid Islam, Behzad M Toosi, Chelsea E Cunningham, Darrell D Mousseau, Maruti C Uppalapati, Peter C Stirling, Yuliang Wu, Keith Bonham, Andrew Freywald, Hui Li, Franco J Vizeacoumar
Chromosomal rearrangements involving the mixed-lineage leukemia (MLL1) gene are common in a unique group of acute leukemias, with more than 100 fusion partners in this malignancy alone. However, do these fusions occur or have a role in solid tumors? We performed extensive network analyses of MLL1-fusion partners in patient datasets, revealing that multiple MLL1-fusion partners exhibited significant interactions with the androgen-receptor signaling pathway. Further exploration of tumor sequence data from TCGA predicts the presence of MLL1 fusions with truncated SET domain in prostate tumors...
December 8, 2018: Molecular Oncology
Yanrong Su, Nathan R Hopfinger, Theresa D Nguyen, Thomas J Pogash, Julia Santucci-Pereira, Jose Russo
BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive neoplasia with no effective therapy. Our laboratory has developed a unique TNBC cell model presenting epithelial mesenchymal transition (EMT) a process known to be important for tumor progression and metastasis. There is increasing evidence showing that epigenetic mechanisms are involved in the activation of EMT. The objective of this study is to epigenetically reverse the process of EMT in TNBC by using DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi)...
December 14, 2018: Journal of Experimental & Clinical Cancer Research: CR
Marion Orsini, Sébastien Chateauvieux, Jiyun Rhim, Anthoula Gaigneaux, David Cheillan, Christo Christov, Mario Dicato, Franck Morceau, Marc Diederich
Elevated levels of the pro-inflammatory cytokine tumor necrosis factor-α (TNFα) inhibit erythropoiesis and cause anemia in patients with cancer and chronic inflammatory diseases. TNFα is also a potent activator of the sphingomyelinase (SMase)/ceramide pathway leading to ceramide synthesis and regulating cell differentiation, proliferation, apoptosis, senescence, and autophagy. Here we evaluated the implication of the TNFα/SMase/ceramide pathway on inhibition of erythropoiesis in human CD34+ hematopoietic stem/progenitor cells (CD34/HSPCs) from healthy donors...
December 13, 2018: Cell Death and Differentiation
Shan Jiang, Natalie Wen, Zeran Li, Umber Dube, Jorge Del Aguila, John Budde, Rita Martinez, Simon Hsu, Maria V Fernandez, Nigel J Cairns, Oscar Harari, Carlos Cruchaga, Celeste M Karch
Mutations in the microtubule-associated protein tau (MAPT) gene cause autosomal dominant frontotemporal lobar degeneration with tau inclusions (FTLD-tau). MAPT p.R406W carriers present clinically with progressive memory loss and neuropathologically with neuronal and glial tauopathy. However, the pathogenic events triggered by the expression of the mutant tau protein remain poorly understood. To identify the genes and pathways that are dysregulated in FTLD-tau, we performed transcriptomic analyses in induced pluripotent stem cell (iPSC)-derived neurons carrying MAPT p...
December 13, 2018: Translational Psychiatry
Valeria Santini
Hypomethylating agents (HMA), azacitidine and decitabine are standard of care for myelodysplastic syndromes. Response to these agents accounts for around 50% of treated patients and duration of response, although variable, is transient. Prediction of response to HMA is possible with clinical and molecular parameters, but alternative approved treatments are not available and in case of HMA failure, there are no standard therapeutic opportunities. It is important to develop a reasoned choice of therapy after HMA failure...
December 13, 2018: Blood
Ruoyu Wu, Jihao Ruan, Yongjin Sun, Mengyu Liu, Zhuang Sha, Cunyi Fan, Qingkai Wu
BACKGROUND: This study was aimed to investigate the role and specific molecular mechanism of HIF1A-AS2/miR-665/IL6 axis in regulating osteogenic differentiation of adipose-derived stem cells (ASCs) via the PI3K/Akt signaling pathway. METHODS: RNAs' expression profile in normal/osteogenic differentiation-induced ASCs (osteogenic group) was from the Gene Expression Omnibus database. The analysis was carried out using Bioconductor of R. Gene Set Enrichment Analysis and Kyoto Encyclopedia of Genes and Genomes dataset were applied to identify up- and downregulated signaling pathways...
December 13, 2018: Stem Cell Research & Therapy
Kuang-Tzu Huang, Li-Wen Hsu, Kuang-Den Chen, Chao-Pin Kung, Shigeru Goto, Chao-Long Chen
Adipogenesis is a tightly regulated cellular process that involves the action of multiple signaling pathways. Characterization of regulators that are associated with adipose development is crucial to understanding the mechanisms underlying obesity and other metabolic disorders. Pigment epithelium-derived factor (PEDF) is a secreted glycoprotein that was first described as a neurotrophic factor. The role of PEDF in lipid metabolism was established when adipose triglyceride lipase (ATGL), a major triglyceride hydrolase, was characterized as its binding partner...
December 11, 2018: International Journal of Molecular Sciences
Tasleem Arif, Avijit Paul, Yakov Krelin, Anna Shteinfer-Kuzmine, Varda Shoshan-Barmatz
Oncogenic properties, along with the metabolic reprogramming necessary for tumour growth and motility, are acquired by cancer cells. Thus, tumour metabolism is becoming a target for cancer therapy. Here, cancer cell metabolism was tackled by silencing the expression of voltage-dependent anion channel 1 (VDAC1), a mitochondrial protein that controls cell energy, as well as metabolic and survival pathways and that is often over-expressed in many cancers. We demonstrated that silencing VDAC1 expression using human-specific siRNA (si-hVDAC1) inhibited cancer cell growth, both in vitro and in mouse xenograft models of human glioblastoma (U-87MG), lung cancer (A549), and triple negative breast cancer (MDA-MB-231)...
December 8, 2018: Cancers
Chi-Hui Sun, Chin-Ying Yang, Jason T C Tzen
Tea ( Camellia sinensis L.) contains abundant secondary metabolites, which are regulated by numerous enzymes. Hydroxycinnamoyl transferase (HCT) is involved in the biosynthesis pathways of polyphenols and flavonoids, and it can catalyze the transfer of hydroxyconnamoyl coenzyme A to substrates such as quinate, flavanol glycoside, or anthocyanins, thus resulting in the production of chlorogenic acid or acylated flavonol glycoside. In this study, the CsHCT gene was cloned from the Chin-Shin Oolong tea plant, and its protein functions and characteristics were analyzed...
December 7, 2018: International Journal of Molecular Sciences
Khaled F Al-Massri, Lamiaa A Ahmed, Hanan S El-Abhar
Peripheral neuropathy is a common adverse effect observed during use of paclitaxel (PTX) as chemotherapy. The present investigation was directed to estimate the modulatory effect of bone marrow derived mesenchymal stem cells (BM-MSCs) on pregabalin (PGB) treatment in PTX-induced peripheral neuropathy. Neuropathic pain was induced in rats by injecting PTX (2 mg/kg, i.p) 4 times every other day. Rats were then treated with PGB (30 mg/kg/day, p.o.) for 21 days with or without a single intravenous administration of BM-MSCs...
December 10, 2018: Behavioural Brain Research
Tiffany J Rios-Fuller, Gabriela Ortiz-Soto, Mercedes Lacourt-Ventura, Gerónimo Maldonado-Martinez, Luis A Cubano, Robert J Schneider, Michelle M Martinez-Montemayor
The aggressive nature of triple negative breast cancer (TNBC) may be explained in part by the presence of breast cancer stem cells (BCSCs), a subpopulation of cells, which are involved in tumor initiation, progression, metastasis, recurrence, and therapy resistance. The signal transducer and activator of transcription 3 (STAT3) pathway participates in the development and progression of BCSCs, but its role in TNBC remains unclear. Here, we report that Ganoderma lucidum extract (GLE), a medicinal mushroom with anticancer activity, acts on BCSCs in vitro and in TNBC pre-clinical animal tumor models by downregulating the STAT3 pathway...
November 13, 2018: Oncotarget
Xinwei Liu, Mingchang Du, Yu Wang, Songbo Liu, Xianmin Liu
Osteoarthritis (OS) is a common disease in orthopedics. Although OS is known as an inflammation mediated by inflammatory cytokines; however, the mechanism is poorly understood. In the present study, the role of bone morphogenetic protein-9 (BMP9) was investigated in chondrogenic differentiation of adipose-derived mesenchymal stem cells (ADMSCs). ADMSCs were transfected with BMP9. BMP9 mRNA expression was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Type II collagen and aggrecan expression was detected by western blotting and RT-qPCR...
December 2018: Experimental and Therapeutic Medicine
Francisco García-Bernal, Noelia Geribaldi-Doldán, Samuel Domínguez-García, Manuel Carrasco, Maribel Murillo-Carretero, Antonio Delgado-Ariza, Mónica Díez-Salguero, Cristina Verástegui, Carmen Castro
Brain injuries of different etiologies lead to irreversible neuronal loss and persisting neuronal deficits. New therapeutic strategies are emerging to compensate neuronal damage upon brain injury. Some of these strategies focus on enhancing endogenous generation of neurons from neural stem cells (NSCs) to substitute the dying neurons. However, the capacity of the injured brain to produce new neurons is limited, especially in cases of extensive injury. This reduced neurogenesis is a consequence of the effect of signaling molecules released in response to inflammation, which act on intracellular pathways, favoring gliogenesis and preventing recruitment of neuroblasts from neurogenic regions...
2018: Frontiers in Cellular Neuroscience
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