scholarly journals The Inhibitory Effects of Terminalia catappa L. Extract on the Migration and Invasion of Human Glioblastoma Multiforme Cells

2021 ◽  
Vol 14 (11) ◽  
pp. 1183
Author(s):  
Hsiao-Hang Chung ◽  
Ming-Ju Hsieh ◽  
Yih-Shou Hsieh ◽  
Pei-Ni Chen ◽  
Chung-Po Ko ◽  
...  
Keyword(s):  
Cell Migration ◽  
Glioblastoma Multiforme ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Migration And Invasion ◽  
Glial Tumor ◽  
Leaf Extracts ◽  
P38 Inhibitor ◽  
Terminalia Catappa ◽  
Mitogen Activated Protein

Glioblastoma multiforme (GBM) is one of the most aggressive and common types of brain tumor. Due to its high proliferation ability, a high lethality rate has been observed with this malignant glial tumor. Terminalia catappa L. (T. catappa) is currently known to have anti-inflammatory and anti-carcinogenesis effects. However, few studies have examined the mechanisms of the leaf extracts of T. catappa (TCE) on GBM cells. In the current study, we demonstrated that TCE can significantly inhibit the migration and invasion capabilities of GBM cell lines without showing biotoxic effects. Matrix metalloproteinases-2 (MMP-2) activity and protein expression were attenuated by reducing the p38 phosphorylation involved in the mitogen-activated protein kinase (MAPK) pathway. By treating with TCE and/or p38 inhibitor (SB203580), we confirmed that p38 MAPK is involved in the inhibition of cell migration. In conclusion, our results demonstrated that TCE inhibits human GBM cell migration and MMP-2 expression by regulating the p38 pathway. These results reveal that TCE contains potent therapeutic compounds which could be applied for treating GBM brain tumors.

scholarly journals p38-Mitogen-Activated Protein Kinase Stimulated Steroidogenesis in Granulosa Cell-Oocyte Cocultures: Role of Bone Morphogenetic Proteins 2 and 4

Endocrinology ◽  
2008 ◽  
Vol 150 (4) ◽  
pp. 1921-1930 ◽  
Author(s):  
Kenichi Inagaki ◽  
Fumio Otsuka ◽  
Tomoko Miyoshi ◽  
Misuzu Yamashita ◽  
Mina Takahashi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Bone Morphogenetic Proteins ◽  
Granulosa Cells ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
P38 Inhibitor ◽  
Morphogenetic Protein ◽  
Progesterone Synthesis ◽  
Mitogen Activated Protein ◽  
Estradiol Synthesis

Roles of the p38-MAPK pathway in steroidogenesis were investigated using coculture of rat granulosa cells with oocytes. Activin and FSH readily phosphorylated p38 in granulosa cells. Activin effect on p38 phosphorylation was abolished by a selective activin receptor-like kinase-4, -5, and -7 inhibitor, SB431542. SB431542 decreased FSH-induced estradiol but had no effect on progesterone production with a marginal cAMP reduction, suggesting that endogenous activin is primarily involved in estradiol synthesis. FSH-induced p38 activation was not affected either by SB431542 or follistatin, suggesting that FSH activates p38 not through the endogenous activin. Bone morphogenetic protein (BMP)-2 and BMP-4 also enhanced FSH-induced p38 phosphorylation, which was augmented by oocyte action. A specific p38 inhibitor, SB203580, decreased FSH-induced estradiol production. However, FSH-induced cAMP accumulation was not changed by SB203580, suggesting that p38 activation is linked to estradiol synthesis independently of cAMP. BMP-2 and BMP-4 inhibited FSH- and forskolin (FSK)-induced progesterone and cAMP synthesis regardless of oocyte action. BMP-2, BMP-4, and activin increased FSH-induced estradiol production, which was enhanced in the presence of oocytes. In contrast to activin that enhanced FSK-induced estradiol, BMP-2 and BMP-4 had no effects on FSK-induced estradiol production, suggesting that BMP-2 and BMP-4 directly activate FSH-receptor signaling. Given that activin increased, but BMP-2 and BMP-4 decreased, FSH-induced cAMP, the effects of BMP-2 and BMP-4 on estradiol enhancement appeared to be diverged from the cAMP-protein kinase A pathway. Thus, BMP-2 and BMP-4 differentially regulate steroidogenesis by stimulating FSH-induced p38 and suppressing cAMP. The former is involved in estradiol production and enhanced by oocyte action, whereas the latter leads to reduction of progesterone synthesis.

scholarly journals Epidermal growth factor-regulated activation of Rac GTPase enhances CD44 cleavage by metalloproteinase disintegrin ADAM10

2006 ◽  
Vol 395 (1) ◽  
pp. 65-71 ◽  
Author(s):  
Toshiyuki Murai ◽  
Takayuki Miyauchi ◽  
Toshio Yanagida ◽  
Yasushi Sako
Keyword(s):  
Cell Migration ◽  
Growth Factor ◽  
Protein Kinase ◽  
Epidermal Growth Factor ◽  
Tumour Cell ◽  
Mitogen Activated Protein Kinase ◽  
Migration And Invasion ◽  
Dominant Negative Mutant ◽  
Mitogen Activated Protein ◽  
Epidermal Growth

Invasive tumour cells, such as gliomas, frequently express EGF (epidermal growth factor) receptor at a high level and they exhibit enhanced cell migration in response to EGF. We reported previously that tumour cell migration is associated with ectodomain cleavage of CD44, the major adhesion molecule that is implicated in tumour invasion and metastasis, and that the cleavage is enhanced by ligation of CD44. In the present study, we show that EGF promotes CD44 cleavage and CD44-dependent cell migration. Introduction of a dominant-negative mutant of the small GTPase Rac1 or depletion of Rac1 by RNAi (RNA interference) abrogated CD44 cleavage induced by EGF. Treatment with PD98059, an inhibitor for MEK (mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase), also suppressed the CD44 cleavage. Furthermore, RNAi studies showed that EGF induced ADAM10 (a disintegrin and metalloproteinase 10)-dependent CD44 cleavage and cell migration. These results indicate that EGF induces ADAM10-mediated CD44 cleavage through Rac1 and mitogen-activated protein kinase activation, and thereby promotes tumour cell migration and invasion.

The NRP1 gene regulates proliferation, apoptosis, migration, and invasion in T24 and 5637 bladder cancer cells

2020 ◽  
Author(s):  
Conghui Han ◽  
Yang Dong ◽  
Lin Hao ◽  
Kun Pang ◽  
Xiaoying Zhang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Molecular Mechanisms ◽  
Biological Function ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Migration And Invasion ◽  
Mapk Signalling Pathway ◽  
Neuropilin 1 ◽  
Mitogen Activated Protein

Abstract Background Bladder urothelial carcinoma (BC) is a fatal invasive malignancy and the most common malignancy of the urinary system. In the current study, we investigate the function and mechanisms of Neuropilin-1 (NRP1), the co-receptor for vascular endothelial growth factor, in BC pathogenesis and progression. Methods The expression of NRP1 was assessed in several BC cell lines. Additionally, the biological function of NRP1 in proliferation, apoptosis, angiogenesis, migration, and invasion of BC were validated in vitro by silencing NRP1. Moreover, gene expression profiling chip analysis was conducted, and the related signalling pathways were confirmed by Western blot to reveal the potential molecular mechanisms by which NRP1 promotes the malignant progression of BC. Results Overexpression of NRP1 was observed in several human BC cell lines. NRP1 knockdown inhibited cell proliferation, promoted apoptosis, and decreased angiogenesis, migration, and invasion in T24 and 5637 human BC cells. Microarray analysis results indicated that the expression of NRP1 was correlated with the levels of cyclin dependent kinase (CDK) 4, baculoviral IAP repeat containing 3, Cyclin E 2, CDK2, and AP-1 transcription factor subunit in BC. We also demonstrated that the biological function of NRP1was associated with activation of the mitogen-activated protein kinase (MAPK) signalling pathway. Conclusions Our findings provide evidence that NRP1, as a potential tumour promoter, contributes to the metastasis and invasion of BC, which is associated with the activation of the MAPK pathway. Targeting NRP1 has the potential to become a new therapeutic strategy to benefit more patients with BC or other cancers.

scholarly journals Ciclopirox and bortezomib synergistically inhibits glioblastoma multiforme growth via simultaneously enhancing JNK/p38 MAPK and NF-κB signaling

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Zhipeng Su ◽  
Shengnan Han ◽  
Qiumei Jin ◽  
Ningning Zhou ◽  
Junwan Lu ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Anticancer Drug ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Cellular Migration ◽  
Mitogen Activated Protein Kinase ◽  
Migration And Invasion ◽  
Mantle Cell ◽  
Mitogen Activated Protein ◽  
Tumorigenic Activity

AbstractCiclopirox (CPX) is an antifungal drug that has recently been reported to act as a potential anticancer drug. However, the effects and underlying molecular mechanisms of CPX on glioblastoma multiforme (GBM) remain unknown. Bortezomib (BTZ) is the first proteasome inhibitor-based anticancer drug approved to treat multiple myeloma and mantle cell lymphoma, as BTZ exhibits toxic effects on diverse tumor cells. Herein, we show that CPX displays strong anti-tumorigenic activity on GBM. Mechanistically, CPX inhibits GBM cellular migration and invasion by reducing N-Cadherin, MMP9 and Snail expression. Further analysis revealed that CPX suppresses the expression of several key subunits of mitochondrial enzyme complex, thus leading to the disruption of mitochondrial oxidative phosphorylation (OXPHOS) in GBM cells. In combination with BTZ, CPX promotes apoptosis in GBM cells through the induction of reactive oxygen species (ROS)-mediated c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) signaling. Moreover, CPX and BTZ synergistically activates nuclear factor kappa B (NF-κB) signaling and induces cellular senescence. Our findings suggest that a combination of CPX and BTZ may serve as a novel therapeutic strategy to enhance the anticancer activity of CPX against GBM.

Tetraspanin CD9 in cell migration

2011 ◽  
Vol 39 (2) ◽  
pp. 563-567 ◽  
Author(s):  
Dale Powner ◽  
Petra M. Kopp ◽  
Susan J. Monkley ◽  
David R. Critchley ◽  
Fedor Berditchevski
Keyword(s):  
Cell Migration ◽  
Focal Adhesion ◽  
Breast Cancer Cells ◽  
Focal Adhesions ◽  
Mitogen Activated Protein Kinase ◽  
Signalling Pathways ◽  
Migration And Invasion ◽  
Mitogen Activated Protein ◽  
Dependent Cell ◽  
Phosphoinositide 3 Kinase

Tetraspanin CD9 is associated with integrin adhesion receptors and it was reported that CD9 regulates integrin-dependent cell migration and invasion. Pro- and anti-migratory effects of CD9 have been linked to adhesion-dependent signalling pathways, including phosphorylation of FAK (focal adhesion kinase) and activation of phosphoinositide 3-kinase, p38 MAPK (mitogen-activated protein kinase) and JNK (c-Jun N-terminal kinase). In the present paper, we describe a novel mechanism whereby CD9 specifically controls localization of talin1, one of the critical regulators of integrin activation, to focal adhesions: CD9-deficiency leads to impaired localization of talin1 to focal adhesions and correlates with increased motility of breast cancer cells.

scholarly journals The Genomic Landscape of Thyroid Cancer Tumourigenesis and Implications for Immunotherapy

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1082
Author(s):  
Amandeep Singh ◽  
Jeehoon Ham ◽  
Joseph William Po ◽  
Navin Niles ◽  
Tara Roberts ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Mapk Pathway ◽  
Treatment Options ◽  
Metastatic Potential ◽  
Pi3k Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Sequencing Data ◽  
Genetic Aberrations ◽  
Progression Model ◽  
Mitogen Activated Protein

Thyroid cancer is the most prevalent endocrine malignancy that comprises mostly indolent differentiated cancers (DTCs) and less frequently aggressive poorly differentiated (PDTC) or anaplastic cancers (ATCs) with high mortality. Utilisation of next-generation sequencing (NGS) and advanced sequencing data analysis can aid in understanding the multi-step progression model in the development of thyroid cancers and their metastatic potential at a molecular level, promoting a targeted approach to further research and development of targeted treatment options including immunotherapy, especially for the aggressive variants. Tumour initiation and progression in thyroid cancer occurs through constitutional activation of the mitogen-activated protein kinase (MAPK) pathway through mutations in BRAF, RAS, mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway and/or receptor tyrosine kinase fusions/translocations, and other genetic aberrations acquired in a stepwise manner. This review provides a summary of the recent genetic aberrations implicated in the development and progression of thyroid cancer and implications for immunotherapy.

Asparanin A inhibits cell migration and invasion in human endometrial cancer via Ras/ERK/MAPK pathway

2021 ◽  
Vol 150 ◽  
pp. 112036 ◽  
Author(s):  
Fan Zhang ◽  
Zhi-Jing Ni ◽  
Lei Ye ◽  
Yuan-Yuan Zhang ◽  
Kiran Thakur ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cell Migration ◽  
Mapk Pathway ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Erk Mapk

Review of treatment and therapeutic targets in brain arteriovenous malformation

2021 ◽  
pp. 0271678X2110267
Author(s):  
Peipei Pan ◽  
Shantel Weinsheimer ◽  
Daniel Cooke ◽  
Ethan Winkler ◽  
Adib Abla ◽  
...  
Keyword(s):  
Animal Models ◽  
De Novo ◽  
Mapk Pathway ◽  
Treatment Options ◽  
Therapeutic Targets ◽  
Current Treatment ◽  
Mitogen Activated Protein Kinase ◽  
De Novo Mutations ◽  
Genetic Syndromes ◽  
Mitogen Activated Protein

Brain arteriovenous malformations (bAVM) are an important cause of intracranial hemorrhage (ICH), especially in younger patients. The pathogenesis of bAVM are largely unknown. Current understanding of bAVM etiology is based on studying genetic syndromes, animal models, and surgically resected specimens from patients. The identification of activating somatic mutations in the Kirsten rat sarcoma viral oncogene homologue (KRAS) gene and other mitogen-activated protein kinase ( MAPK) pathway genes has opened up new avenues for bAVM study, leading to a paradigm shift to search for somatic, de novo mutations in sporadic bAVMs instead of focusing on inherited genetic mutations. Through the development of new models and understanding of pathways involved in maintaining normal vascular structure and functions, promising therapeutic targets have been identified and safety and efficacy studies are underway in animal models and in patients. The goal of this paper is to provide a thorough review or current diagnostic and treatment tools, known genes and key pathways involved in bAVM pathogenesis to summarize current treatment options and potential therapeutic targets uncovered by recent discoveries.

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