scholarly journals The Delta intracellular domain mediates TGF-β/Activin signaling through binding to Smads and has an important bi-directional function in the Notch–Delta signaling pathway

2007 ◽  
Vol 35 (3) ◽  
pp. 912-922 ◽  
Author(s):  
Masahiro Hiratochi ◽  
Hisashi Nagase ◽  
Yu Kuramochi ◽  
Chang-Sung Koh ◽  
Takeshi Ohkawara ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Intracellular Domain ◽  
Activin Signaling

scholarly journals Dual Roles of the Activin Signaling Pathway in Pancreatic Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 821
Author(s):  
Wanglong Qiu ◽  
Chia-Yu Kuo ◽  
Yu Tian ◽  
Gloria H. Su
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Critical Role ◽  
Genetic Mutations ◽  
Cancer Genetic ◽  
Dual Roles ◽  
Activin Signaling ◽  
Physiological Processes ◽  
Cancer Types ◽  
Related Proteins

Activin, a member of the TGF-β superfamily, is involved in many physiological processes, such as embryonic development and follicle development, as well as in multiple human diseases including cancer. Genetic mutations in the activin signaling pathway have been reported in many cancer types, indicating that activin signaling plays a critical role in tumorigenesis. Recent evidence reveals that activin signaling may function as a tumor-suppressor in tumor initiation, and a promoter in the later progression and metastasis of tumors. This article reviews many aspects of activin, including the signaling cascade of activin, activin-related proteins, and its role in tumorigenesis, particularly in pancreatic cancer development. The mechanisms regulating its dual roles in tumorigenesis remain to be elucidated. Further understanding of the activin signaling pathway may identify potential therapeutic targets for human cancers and other diseases.

scholarly journals Alantolactone Inhibits Cell Proliferation by Interrupting the Interaction between Cripto-1 and Activin Receptor Type II A in Activin Signaling Pathway

2011 ◽  
Vol 16 (5) ◽  
pp. 525-535 ◽  
Author(s):  
Ying Shi ◽  
Yong Li Bao ◽  
Yin Wu ◽  
Chun Lei Yu ◽  
Yan Xin Huang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Tumor Formation ◽  
Receptor Type ◽  
Type Ii ◽  
Activin Receptor ◽  
Activin Signaling ◽  
Two Hybrid ◽  
Beneficial Approach

It has been suggested that deregulation of activin signaling contributes to tumor formation. Activin signaling is blocked in cancer cells due to the complex formed by Cripto-1, activin, and activin receptor type II (ActRII). In this study, the authors used a mammalian two-hybrid system to construct a drug screening model to obtain a small molecular inhibitor capable of interrupting the interaction between Cripto-1 and ActRII. They screened 300 natural components and identified alantolactone. Data suggested that alantolactone induced activin/SMAD3 signaling in human colon adenocarcinoma HCT-8 cells. The authors also found that alantolactone exhibited antiproliferative function specific to tumor cells, with almost no toxicity to normal cells at a concentration of 5 µg/mL. Furthermore, they proved that the antiproliferative function of alantolactone was activin/SMAD3 dependent. These results suggest that alantolactone performs its antitumor effect by interrupting the interaction between Cripto-1 and the activin receptor type IIA in the activin signaling pathway. Moreover, screening for inhibitors of Cripto-1/ActRII is a potentially beneficial approach to aid in discovering novel cancer treatment.

Usefulness of peripheral regulatory T-cells induced by Notch signaling pathway-driven indoleamine 2, 3-dioxygenase positive dendritic cell as a biomarker for the decision for IPMN surgical indications.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 181-181
Author(s):  
Tetsuya Ikemoto ◽  
Mitsuo Shimada ◽  
Toru Utsunomiya ◽  
Yuji Morine ◽  
Satoru Imura ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Peripheral Blood ◽  
Notch Signaling Pathway ◽  
Clinicopathological Factors ◽  
Surgical Indications ◽  
Intracellular Domain ◽  
Indoleamine 2

181 Background: This study was performed to elucidate the expression of the Notch signaling pathway regulated by dendetric cell (DC) and their correlations to clinicopathological factors of intraductal papillary mucinous neoplasms (IPMNs) as a new biomarker for surgical indications. We already reported that regulatory T cells (Tregs) play an important role in tumor immunity (Pancreas 2006, ASCO-GI 2009), however, the whole mechanism of control of peripheral Tregs remains unclear. It is reported that Indoleamine 2, 3-dioxygenase (IDO) induces active Treg from naïve CD4+Tcells through dendritic cells. Otherwise, we also reported that the Notch signaling pathway is involved in tumor growth and DC function (JI 2010). Thus we focused that Indoleamine 2,3-deoxygenase(IDO)-Treg axis driven by Notch signaling in IPMNs. Methods: Peripheral blood samples and resected specimens from 20 patients with IPMN were evaluated. All patients were pathologically diagnosed with IPMN. Resected specimens were immunohistochemically evaluated (anti-Notch1, anti-Notch2, anti-Notch2-intracellular domain and anti-IDO antibody staining) and compared to clinicopathological factors. Peripheral Treg populations were analyzed with an automated flow cytometer. Results: Disease-free survival was significantly worse in the Notch1 high-expression group (P<0.05). Notch2 family expressions were higher in intraductal papillary mucinous carcinoma (IPMC) than in intraductal papillary mucinous adenoma (IPMA) (Notch2, P< 0.05; Notch2-intracellular domain, P < 0.05). Jagged1 and IDO expressions were significantly higher in IPMC than in IPMA (P < 0.05) and was significantly related to recurrence. The Treg population in peripheral blood was higher in patients with IPMC than in those with IPMA (P < 0.01). Conclusions: Notch signaling, especially Jagged1 expression, regulated by IDO+DC reflects IPMN aggressiveness. Our data strongly suggest that peripheral Treg induced by Notch signaling pathway driven IDO+DC may be a nobel biomarker for the decision for IPMN surgical indications.

miR-181a promotes porcine granulosa cell apoptosis by targeting TGFBR1 via the activin signaling pathway

2020 ◽  
Vol 499 ◽  
pp. 110603 ◽  
Author(s):  
Jia-Qing Zhang ◽  
Bin-Wen Gao ◽  
Hong-Xia Guo ◽  
Qiao-Ling Ren ◽  
Xian-Wei Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Granulosa Cell ◽  
Cell Apoptosis ◽  
Activin Signaling ◽  
Porcine Granulosa Cell

scholarly journals Role of satellite cells versus myofibers in muscle hypertrophy induced by inhibition of the myostatin/activin signaling pathway

2012 ◽  
Vol 109 (35) ◽  
pp. E2353-E2360 ◽  
Author(s):  
S.-J. Lee ◽  
T. V. Huynh ◽  
Y.-S. Lee ◽  
S. M. Sebald ◽  
S. A. Wilcox-Adelman ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Satellite Cells ◽  
Muscle Hypertrophy ◽  
Activin Signaling

scholarly journals MicroRNA-449a Inhibition Protects H9C2 Cells Against Hypoxia/Reoxygenation-Induced Injury by Targeting the Notch-1 Signaling Pathway

2018 ◽  
Vol 46 (6) ◽  
pp. 2587-2600 ◽  
Author(s):  
Jing Cheng ◽  
Qianfu Wu ◽  
Rong Lv ◽  
Li Huang ◽  
Banglong Xu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cell Injury ◽  
Ventricular Myocytes ◽  
Neonatal Rat ◽  
H9c2 Cells ◽  
Notch 1 ◽  
Intracellular Domain ◽  
Rat Ventricular Myocytes ◽  
Neonatal Rat Ventricular Myocytes ◽  
Hypoxia Reoxygenation

Background/Aims: The present study aimed to detect the expression of miR-449a and investigate the effect of miR-449a on cell injury in cardiomyocytes subjected to hypoxia/ reoxygenation (H/R) and its underlying mechanisms. Methods: The expression of miR-449a was determined using reverse transcription–polymerase chain reaction in both neonatal rat ventricular myocytes and H9C2 cells. For gain-of-function and loss-of-function studies, H9C2 cells were transfected with either miR-449a mimics or miR-449a inhibitor. The target gene of miR-449a was confirmed by a dual-luciferase reporter assay. Apoptosis was analyzed by both flow cytometry using Annexin V and propidium iodide and transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL). Necrosis was confirmed by the detection of lactate dehydrogenase release. The cell viability was measured using the methylthiotetrazole method. The protein levels of Notch-1, Notch-1 intracellular domain, hairy and enhancer of split-1 (Hes-1), and apoptosis-related genes were measured by Western blot analysis. Results: MiR-449a was significantly upregulated in both neonatal rat ventricular myocytes and H9C2 cells subjected to H/R. However, H/R-induced cell apoptosis and necrosis were markedly reduced by miR-449a inhibition. By targeting Notch-1, miR-449a regulated the Notch-1/ Hes-1 signaling pathway. The blockade of the Notch signaling pathway partly abolished the protective effect of miR-449a suppression against H/R injury, whereas the overexpression of Notch-1 intracellular domain partly reversed the effect of miR-449a overexpression on H/R-induced cell injury. Conclusions: The present study suggested that miR-449a inhibition protected H9C2 cells against H/R-induced cell injury by targeting the Notch-1 signaling pathway, providing a novel insight into the molecular basis of myocardial ischemia–reperfusion injury and a potential therapeutic target.

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