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https://www.readbyqxmd.com/read/28163723/activin-a-modulates-cripto-1-hnf4%C3%AE-cells-to-guide-cardiac-differentiation-from-human-embryonic-stem-cells
#1
Robin Duelen, Guillaume Gilbert, Abdulsamie Patel, Nathalie de Schaetzen, Liesbeth De Waele, Llewelyn Roderick, Karin R Sipido, Catherine M Verfaillie, Gunnar M Buyse, Lieven Thorrez, Maurilio Sampaolesi
The use of human pluripotent stem cells in basic and translational cardiac research requires efficient differentiation protocols towards cardiomyocytes. In vitro differentiation yields heterogeneous populations of ventricular-, atrial-, and nodal-like cells hindering their potential applications in regenerative therapies. We described the effect of the growth factor Activin A during early human embryonic stem cell fate determination in cardiac differentiation. Addition of high levels of Activin A during embryoid body cardiac differentiation augmented the generation of endoderm derivatives, which in turn promoted cardiomyocyte differentiation...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28126904/biochemical-and-cellular-analysis-reveals-ligand-binding-specificities-a-molecular-basis-for-ligand-recognition-and-membrane-association-dependent-activities-of-cripto-1-and-cryptic
#2
Senem Aykul, Anthony Parenti, Kit Yee Chu, Jake Reske, Monique Floer, Amy Ralston, Erik Martinez-Hackert
Transforming growth factor β (TGF-β) pathways are key determinants of cell fate in animals. Their basic mechanism of action is simple. However, to produce cell-specific responses, TGF-β pathways are heavily regulated by secondary factors, such as membrane-associated EGF-CFC family proteins. Cellular activities of EGF-CFC proteins have been described, but their molecular functions, including how the mammalian homologs Cripto-1 and Cryptic recognize and regulate TGF-β family ligands, are less clear. Here we use purified human Cripto-1 and mouse Cryptic produced in mammalian cells to show that these two EGF-CFC homologs have distinct, highly specific ligand binding activities...
March 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28118982/sox4-regulates-gonad-morphogenesis-and-promotes-male-germ-cell-differentiation-in-mice
#3
Liang Zhao, Michel Arsenault, Ee Ting Ng, Enya Longmuss, Tevin Chui-Ying Chau, Sunny Hartwig, Peter Koopman
The group C SOX transcription factors SOX4, -11 and -12 play important and mutually overlapping roles in development of a number of organs. Here, we examined the role of SoxC genes during gonadal development in mice. All three genes were expressed in developing gonads of both sexes, predominantly in somatic cells, with Sox4 being most strongly expressed. Sox4 deficiency resulted in elongation of both ovaries and testes, and an increased number of testis cords. While female germ cells entered meiosis normally, male germ cells showed reduced levels of differentiation markers Nanos2 and Dnmt3l and increased levels of pluripotency genes Cripto and Nanog, suggesting that SOX4 may normally act to restrict the pluripotency period of male germ cells and ensure their proper differentiation...
March 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28098905/cripto-1-promotes-epithelial-mesenchymal-transition-in-prostate-cancer-via-wnt-%C3%AE-catenin-signaling
#4
Yan Liu, Zhenbang Qin, Kuo Yang, Ranlu Liu, Yong Xu
The Cripto-1 (CR-1) derived EGF-CFC family was overexpressed in tumor development enhancing proliferation, epithelial-mesenchymal transition (EMT) and migration of tumor cells. However, correlation between CR-1 and prostate cancer (PCa) remains still unclear. In the present study, we proved that CR-1 was expressed in PCa and its function was in the progression of PCa. Compared with benign prostatic hyperplasia (BPH) tissues, we confirmed that PCa tissues had high expression of CR-1 by immunohistochemistry and statistical data showed that CR-1 promoted properties of EMT in PCa tissues, including the downregulation of the cell adhesion molecules β-catenin (membrane) and E-cadherin while upregulating transcription factors β-catenin...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/27881714/a-gpi-processing-phospholipase-a2-pgap6-modulates-nodal-signaling-in-embryos-by-shedding-cripto
#5
Gun-Hee Lee, Morihisa Fujita, Katsuyoshi Takaoka, Yoshiko Murakami, Yoshitaka Fujihara, Noriyuki Kanzawa, Kei-Ichi Murakami, Eriko Kajikawa, Yoko Takada, Kazunobu Saito, Masahito Ikawa, Hiroshi Hamada, Yusuke Maeda, Taroh Kinoshita
Glycosylphosphatidylinositol-anchored proteins (GPI-APs) can be shed from the cell membrane by GPI cleavage. In this study, we report a novel GPI-processing enzyme, termed post-glycosylphosphatidylinositol attachment to proteins 6 (PGAP6), which is a GPI-specific phospholipase A2 mainly localized at the cell surface. CRIPTO, a GPI-AP, which plays critical roles in early embryonic development by acting as a Nodal coreceptor, is a highly sensitive substrate of PGAP6, whereas CRYPTIC, a close homologue of CRIPTO, is not sensitive...
December 5, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27687577/ectopic-expression-of-cripto-1-in-transgenic-mouse-embryos-causes-hemorrhages-fatal-cardiac-defects-and-embryonic-lethality
#6
Xiaolin Lin, Wentao Zhao, Junshuang Jia, Taoyan Lin, Gaofang Xiao, Shengchun Wang, Xia Lin, Yu Liu, Li Chen, Yujuan Qin, Jing Li, Tingting Zhang, Weichao Hao, Bangzhu Chen, Raoying Xie, Yushuang Cheng, Kang Xu, Kaitai Yao, Wenhua Huang, Dong Xiao, Yan Sun
Targeted disruption of Cripto-1 in mice caused embryonic lethality at E7.5, whereas we unexpectedly found that ectopic Cripto-1 expression in mouse embryos also led to embryonic lethality, which prompted us to characterize the causes and mechanisms underlying embryonic death due to ectopic Cripto-1 expression. RCLG/EIIa-Cre embryos displayed complex phenotypes between embryonic day 14.5 (E14.5) and E17.5, including fatal hemorrhages (E14.5-E15.5), embryo resorption (E14.5-E17.5), pale body surface (E14.5-E16...
September 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27586544/cripto-is-essential-to-capture-mouse-epiblast-stem-cell-and-human-embryonic-stem-cell-pluripotency
#7
Alessandro Fiorenzano, Emilia Pascale, Cristina D'Aniello, Dario Acampora, Cecilia Bassalert, Francesco Russo, Gennaro Andolfi, Mauro Biffoni, Federica Francescangeli, Ann Zeuner, Claudia Angelini, Claire Chazaud, Eduardo J Patriarca, Annalisa Fico, Gabriella Minchiotti
Known molecular determinants of developmental plasticity are mainly transcription factors, while the extrinsic regulation of this process has been largely unexplored. Here we identify Cripto as one of the earliest epiblast markers and a key extracellular determinant of the naive and primed pluripotent states. We demonstrate that Cripto sustains mouse embryonic stem cell (ESC) self-renewal by modulating Wnt/β-catenin, whereas it maintains mouse epiblast stem cell (EpiSC) and human ESC pluripotency through Nodal/Smad2...
2016: Nature Communications
https://www.readbyqxmd.com/read/27467944/cripto-1-vaccination-elicits-protective-immunity-against-metastatic-melanoma
#8
M A Ligtenberg, K Witt, F Galvez-Cancino, A Sette, A Lundqvist, A Lladser, R Kiessling
Metastatic melanoma is a fatal disease that responds poorly to classical treatments but can be targeted by T cell-based immunotherapy. Cancer vaccines have the potential to generate long-lasting cytotoxic CD8(+) T cell responses able to eradicate established and disseminated tumors. Vaccination against antigens expressed by tumor cells with enhanced metastatic potential represents a highly attractive strategy to efficiently target deadly metastatic disease. Cripto-1 is frequently over-expressed in human carcinomas and melanomas, but is expressed only at low levels on normal differentiated tissues...
May 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27446436/translational-significance-of-nodal-cripto-1-and-notch4-in-adult-nevi
#9
Luigi Strizzi, Naira V Margaryan, Pedram Gerami, Zahra Haghighat, Paul W Harms, Gabriele Madonna, Gerardo Botti, Paolo A Ascierto, Mary J C Hendrix
The TGF-β associated growth factor Nodal is highly expressed in aggressive metastatic melanoma. Determining the risk for melanomagenesis from Nodal expression in nevi prior to the development of melanoma may be useful for both the screening and prevention of melanoma. Tissue sections of human adult nevi with or without a history of melanoma were stained by immunohistochemistry (IHC) for Nodal, the Nodal co-receptor Cripto-1, and Notch4, which have previously been shown to be associated with Nodal expression in melanoma...
August 2016: Oncology Letters
https://www.readbyqxmd.com/read/27444932/aptamer-based-proteomic-profiling-reveals-novel-candidate-biomarkers-and-pathways-in-cardiovascular-disease
#10
Debby Ngo, Sumita Sinha, Dongxiao Shen, Eric W Kuhn, Michelle J Keyes, Xu Shi, Mark D Benson, John F O'Sullivan, Hasmik Keshishian, Laurie A Farrell, Michael A Fifer, Ramachandran S Vasan, Marc S Sabatine, Martin G Larson, Steven A Carr, Thomas J Wang, Robert E Gerszten
BACKGROUND: Single-stranded DNA aptamers are oligonucleotides of ≈50 base pairs in length selected for their ability to bind proteins with high specificity and affinity. Emerging DNA aptamer-based technologies may address limitations of existing proteomic techniques, including low sample throughput, which have hindered proteomic analyses of large cohorts. METHODS: To identify early biomarkers of myocardial injury, we applied an aptamer-based proteomic platform that measures 1129 proteins to a clinically relevant perturbational model of planned myocardial infarction (PMI), patients undergoing septal ablation for hypertrophic cardiomyopathy...
July 26, 2016: Circulation
https://www.readbyqxmd.com/read/27273137/analysis-of-extraembryonic-mesodermal-structure-formation-in-the-absence-of-morphological-primitive-streak
#11
Jiu-Zhen Jin, Yuanqi Zhu, Dennis Warner, Jixiang Ding
During mouse gastrulation, the primitive streak is formed on the posterior side of the embryo. Cells migrate out of the primitive streak to form the future mesoderm and endoderm. Fate mapping studies revealed a group of cell migrate through the proximal end of the primitive streak and give rise to the extraembryonic mesoderm tissues such as the yolk sac blood islands and allantois. However, it is not clear whether the formation of a morphological primitive streak is required for the development of these extraembryonic mesodermal tissues...
August 2016: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/27082313/microrna-15b-suppresses-the-growth-and-invasion-of-glioma-cells-through-targeted-inhibition-of-cripto-1-expression
#12
Guan Sun, Shu-Shan Yan, Lei Shi, Zheng-Qiang Wan, Nan Jiang, Lin-Shan Fu, Min Li, Jun Guo
Gliomas are the most common type of malignant brain tumor. Studies have identified that miR‑15b is negatively correlated with cripto-1 expression in glioma cells, and these molecules serve an important role in cancer development and progression. The current study was undertaken to further examine the association between these two molecules. Fluorescent quantitative PCR confirmed that miR‑15b expression was significantly downregulated in glioma tissue while cripto‑1 expression was significantly increased...
June 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/26968398/developmental-signaling-pathways-regulating-mammary-stem-cells-and-contributing-to-the-etiology-of-triple-negative-breast-cancer
#13
REVIEW
Maria Cristina Rangel, Daniel Bertolette, Nadia P Castro, Malgorzata Klauzinska, Frank Cuttitta, David S Salomon
Cancer has been considered as temporal and spatial aberrations of normal development in tissues. Similarities between mammary embryonic development and cell transformation suggest that the underlying processes required for mammary gland development are also those perturbed during various stages of mammary tumorigenesis and breast cancer (BC) development. The master regulators of embryonic development Cripto-1, Notch/CSL, and Wnt/β-catenin play key roles in modulating mammary gland morphogenesis and cell fate specification in the embryo through fetal mammary stem cells (fMaSC) and in the adult organism particularly within the adult mammary stem cells (aMaSC), which determine mammary progenitor cell lineages that generate the basal/myoepithelial and luminal compartments of the adult mammary gland...
April 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/26811383/mef2c-regulates-outflow-tract-alignment-and-transcriptional-control-of-tdgf1
#14
Ralston M Barnes, Ian S Harris, Eric J Jaehnig, Kimberly Sauls, Tanvi Sinha, Anabel Rojas, William Schachterle, David J McCulley, Russell A Norris, Brian L Black
Congenital heart defects are the most common birth defects in humans, and those that affect the proper alignment of the outflow tracts and septation of the ventricles are a highly significant cause of morbidity and mortality in infants. A late differentiating population of cardiac progenitors, referred to as the anterior second heart field (AHF), gives rise to the outflow tract and the majority of the right ventricle and provides an embryological context for understanding cardiac outflow tract alignment and membranous ventricular septal defects...
March 1, 2016: Development
https://www.readbyqxmd.com/read/26654129/cripto-expression-epigenetic-regulation-and-potential-diagnostic-use-in-testicular-germ-cell-tumors
#15
Cassy M Spiller, Ad J M Gillis, Guillaume Burnet, Hans Stoop, Peter Koopman, Josephine Bowles, Leendert H J Looijenga
Type II germ cell tumors arise after puberty from a germ cell that was incorrectly programmed during fetal life. Failure of testicular germ cells to properly differentiate can lead to the formation of germ cell neoplasia in situ of the testis; this precursor cell invariably gives rise to germ cell cancer after puberty. The Nodal co-receptor Cripto is expressed transiently during normal germ cell development and is ectopically expressed in non-seminomas that arise from germ cell neoplasia in situ, suggesting that its aberrant expression may underlie germ cell dysregulation and hence germ cell cancer...
April 2016: Molecular Oncology
https://www.readbyqxmd.com/read/26605871/serum-cripto-1-is-a-novel-biomarker-for-non-small-cell-lung-cancer-diagnosis-and-prognosis
#16
Chun Hua Xu, Yan Wang, Li Hua Qian, Li Ke Yu, Xiu Wei Zhang, Qing Bo Wang
INTRODUCTION: Cripto-1 (CR-1) is highly expressed in several different types of human tumors. However, the clinical significance of CR-1 expression in serum specimens from non-small cell lung cancer (NSCLC) patients has not yet been determined. OBJECTIVES: The aim of this study was to explore the diagnostic and prognostic value of serum CR-1 levels in patients with NSCLC. METHODS: Serum specimens from 592 NSCLC patients, 180 benign lung disease patients, and 240 healthy controls were collected...
November 25, 2015: Clinical Respiratory Journal
https://www.readbyqxmd.com/read/26476731/cripto-1-modulates-macrophage-cytokine-secretion-and-phagocytic-activity-via-nf-%C3%AE%C2%BAb-signaling
#17
Dong-mei Zhang, Yong-Li Bao, Chun-Lei Yu, Yi-meng Wang, Zhen-Bo Song
Cripto-1 is an oncogenic protein belonging to the epidermal growth factor–Cripto-1/FRL-1/Cryptic family. It has important roles in tumor formation and metastasis, but its effects on the immune system are unclear. In the present study, we investigated the effects of Cripto-1 overexpression on macrophage activities and examined the underlying mechanisms. A cell line stably overexpressing Cripto-1 was developed. The culture supernatant from this cell line was collected and used to condition macrophages (RAW264...
February 2016: Immunologic Research
https://www.readbyqxmd.com/read/26472984/cripto-1-promotes-the-epithelial-mesenchymal-transition-in-esophageal-squamous-cell-carcinoma-cells
#18
Chun Huang, Wangsheng Chen, Xiaowen Wang, Jinqiu Zhao, Qian Li, Zhongxue Fu
Esophageal carcinoma is a major public health problem worldwide and one of the most aggressively malignant neoplasms. Although considerable diagnostic and therapeutic progress has been made in recent years, the prognosis of EC patients still remains dismal due to high rates of recurrence/metastasis and invasion. Previous studies have demonstrated that Epithelial mesenchymal transition (EMT) is proposed as a critical mechanism for the acquisition of malignant phenotypes by epithelial cells. Several lines of evidence have shown that Cripto-1 plays an important oncogenic role during tumorigenesis by promoting EMT...
2015: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/26375669/elevated-expression-of-cripto-1-correlates-with-poor-prognosis-in-hepatocellular-carcinoma
#19
Jia-Hong Wang, Wei Wei, Jing Xu, Zhi-Xing Guo, Cheng-Zuo Xiao, Yong-Fa Zhang, Pei-En Jian, Xiao-Liang Wu, Ming Shi, Rong-Ping Guo
Cripto-1 could promote tumorigenesis in a wide range of carcinomas, yet little is known in hepatocellular carcinoma (HCC). The expression of Cripto-1 and MMP-9 were assessed by immunohistochemistry in 205 HCC specimens. The correlation between Cripto-1 and MMP-9, clinicopathological/prognostic value in HCC was examined. Cripto-1 overexpression was correlated with larger tumor, TNM stage, BCLC stage and tumor recurrence. In multivariate analyses, Cripto-1 was an independent predictor for overall survival (OS) and time to recurrence (TTR)...
October 27, 2015: Oncotarget
https://www.readbyqxmd.com/read/26370966/new-anti-nodal-monoclonal-antibodies-targeting-the-nodal-pre-helix-loop-involved-in-cripto-1-binding
#20
Annalia Focà, Luca Sanguigno, Giuseppina Focà, Luigi Strizzi, Roberta Iannitti, Rosanna Palumbo, Mary J C Hendrix, Antonio Leonardi, Menotti Ruvo, Annamaria Sandomenico
Nodal is a potent embryonic morphogen belonging to the TGF-β superfamily. Typically, it also binds to the ALK4/ActRIIB receptor complex in the presence of the co-receptor Cripto-1. Nodal expression is physiologically restricted to embryonic tissues and human embryonic stem cells, is absent in normal cells but re-emerges in several human cancers, including melanoma, breast, and colon cancer. Our aim was to obtain mAbs able to recognize Nodal on a major CBR (Cripto-Binding-Region) site and to block the Cripto-1-mediated signalling...
September 7, 2015: International Journal of Molecular Sciences
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