A5061244868- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Protein Kinase Regulation and GTPase Signaling
- Epigenetics and DNA Methylation
- Cell Adhesion Molecules Research
- Cancer Immunotherapy and Biomarkers
- Pancreatic and Hepatic Oncology Research
- RNA Research and Splicing
- Phagocytosis and Immune Regulation
- Melanoma and MAPK Pathways
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Protease and Inhibitor Mechanisms
- Cancer-related Molecular Pathways
- Peptidase Inhibition and Analysis
- HER2/EGFR in Cancer Research
- Cellular transport and secretion
- Cancer Cells and Metastasis
- T-cell and B-cell Immunology
- Cell death mechanisms and regulation
- Signaling Pathways in Disease
- NF-κB Signaling Pathways
- Endoplasmic Reticulum Stress and Disease
- Monoclonal and Polyclonal Antibodies Research
- Receptor Mechanisms and Signaling
Hokkaido University
2014-2024
Osaka International University
2019
Osaka University
2004-2019
McGill University
2019
Daido University
2010
Osaka Science Museum
2008
Nagoya University
2004
Kyoto University
2004
Kansai Medical University
1998-2003
Columbia University
1998
In most human breast cancer cell lines, there is a direct correlation between their in vivo invasive phenotypes and vitro invasion activities. Here, we found that ADP-ribosylation factor 6 (Arf6) localized at the invadopodia of cultured cells MDA-MB-231, its suppression by small-interfering RNA duplex effectively blocks activities cells, such as formation, matrix degradation Matrigel transmigration but not cell-adhesion activity. We also GTP hydrolysis-defective mutant Arf6(Q67L) GTP-binding...
Mitogen-activated protein (MAP) kinase family members, including extracellular signal–regulated (ERK), c-Jun NH2-terminal ( JNK), and p38 MAP kinase, have been implicated in coupling the B cell antigen receptor (BCR) to transcriptional responses. However, mechanisms that lead activation of these members poorly elucidated. Here we demonstrate BCR-induced ERK is reduced by loss Grb2 or expression a dominant-negative form Ras, RasN17, whereas this response not affected Shc. The inhibition was...
Significance Pancreatic ductal carcinomas (PDACs) have been extensively studied regarding their genomic alterations, microenvironmental intercommunication, and metabolic reprogramming. However, identification of the protein machinery tumor cells that eventually drives malignancy as a result driver mutations, associated events, is highly anticipated toward development precision medicine. The lack such information PDACs has hindered elucidation mechanisms driving malignancies, leaving them...
Abstract Acquisition of mesenchymal properties by cancer cells is critical for their malignant behaviour, but regulators the molecular machinery and how it activated remain elusive. Here we show that clear cell renal carcinomas (ccRCCs) frequently utilize Arf6-based pathway to promote invasion metastasis, similar breast cancers. In cells, ligand-activated receptor tyrosine kinases employ GEP100 activate Arf6, which then recruits AMAP1; AMAP1 binds mesenchymal-specific protein EPB41L5,...
Abstract Cross-linking of the B cell Ag receptor (BCR) induces tyrosine phosphorylation multiple cellular substrates, including phospholipase C (PLC)-γ2, which is involved in activation phosphatidylinositol pathway. To assess importance PLC-γ2 murine lymphopoiesis, gene was inducibly ablated by using IFN-regulated Cre recombinase. Mice with a neonatally induced loss function displayed reduced numbers mature conventional cells and peritoneal B1 defective responses vitro to BCR stimulation...
Epidermal growth factor receptor (EGFR) signaling is one of the crucial factors in breast cancer malignancy. Breast cells often overexpress Arf6 and its effector, AMAP1/ASAP1/DDEF1; these cells, EGFR may activate pathway to induce invasion metastasis. Active recycling some integrins for Here, we show that Arf6-AMAP1 links machinery recycles β1 integrins, such as α3β1, promote cell upon stimulation. We found AMAP1 had ability bind directly PRKD2 hence make a complex with cytoplasmic tail...
Two important Ras guanine nucleotide exchange factors, Son of sevenless (Sos) and releasing protein (RasGRP), have been implicated in controlling activation when cell surface receptors are stimulated. To address the specificity or redundancy these we generated Sos1/Sos2 double- RasGRP3-deficient B lines determined their ability to mediate upon receptor (BCR) stimulation. The BCR requires RasGRP3; contrast, epidermal growth factor is dependent on Sos1 Sos2. Furthermore, show that BCR-induced...
Invasive potentials of carcinomas greatly contribute to their metastasis, which is a major threat in most cancers. We have recently shown that Arf6 plays pivotal role breast cancer invasive activities and identified AMAP1 as an effector GTP-Arf6 invasion. Expression correlates well with phenotypes primary tumors the human breast. also functions by forming trimeric protein complex cortactin paxillin. In this complex, binds src homology 3 (SH3) domain via its proline-rich peptide,...
Angiogenesis and cancer invasiveness greatly contribute to malignancy. Arf6 its effector, AMAP1, are frequently overexpressed in breast cancer, constitute a central pathway induce the invasion metastasis. In this pathway, is activated by EGFR via GEP100. highly expressed also human umbilical vein endothelial cells (HUVECs) implicated angiogenesis. Here, we found that HUVECs express vascular growth factor receptor-2 (VEGFR2) recruits GEP100 activate Arf6. AMAP1 functions binding cortactin We...
Drug resistance, metastasis, and a mesenchymal transcriptional program are central features of aggressive breast tumors. The GTPase Arf6, often overexpressed in tumors, is critical to promote epithelial–mesenchymal transition invasiveness. metabolic mevalonate pathway (MVP) associated with tumor invasiveness known prenylate proteins, but which prenylated proteins for MVP-driven cancers unknown. We show here that MVP requires the Arf6-dependent program. enzyme geranylgeranyl transferase II...
Onset of the cancer mesenchymal program is closely associated with malignancy and drug resistance. Among different epithelial-mesenchymal transition (EMT)-associated transcriptional factors, ZEB1 has a key role in inducing phenotypes stem cell-like properties breast cells. ARF6 its effector AMAP1 are frequently overexpressed cells, promote invasion, metastasis EPB41L5 induced during EMT, mediates disruption E-cadherin-based cell-cell adhesion promotion focal dynamics. Here we show that an...
The small GTPase Arf6 and its downstream effector AMAP1 (also called ASAP1/DDEF1) constitute a signaling pathway promoting cell invasion, in which interacts with several different proteins, including PRKD2, EPB41L5, paxillin, cortactin. Components of this are often overexpressed human breast cancer cells, to be correlated poor prognosis the patients, whereas overexpression did not correlate four main molecular classes tumors. In pathway, receptor tyrosine kinases, EGFR Her2, activate via...
Overexpression of Her2/ErbB2/Neu in cancer is often correlated with recurrent distant metastasis, although the mechanism still remains largely elusive. We have previously shown that EGFR, when tyrosine-phosphorylated, binds to GEP100/BRAG2 activate Arf6, which induces invasion and metastasis. now show overexpressed Her2 lung adenocarcinoma cells also employs GEP100. Like EGFR-GEP100 binding, this association primarily mediated by pleckstrin homology (PH) domain GEP100 Tyr1139/Tyr1196 Her2....
Despite recent advances in cancer therapeutics general, the survival of patients with head and neck squamous cell carcinomas (HNSCCs) has not improved substantially over past few decades. HNSCC cells often exhibit invasive metastatic phenotypes, expression epidermal growth factor receptor (EGFR) cortactin been highly implicated development malignancy HNSCCs. We have shown previously that an Arf6 pathway, which is activated by GEP100 employs AMAP1 (also called DDEF1 or ASAP1) as its...
Two signaling pathways known to be essential for progression from immature mature B cells are BAFF receptor (BAFF-R) and the cell (BCR). Here, we first show that phospholipase C (PLC)-γ2 is required a BAFF-R–mediated survival signal. Then, have examined question of whether reduced number in PLC-γ2−/− mice caused by defect either BCR or BAFF-R signaling. We find PLC-γ2 SH2 mutant, which inhibits coupling between PLC-γ2, fails restore maturation, despite supporting BAFF-dependent survival....
The acquisition of mesenchymal traits leads to immune evasion in various cancers, but the underlying molecular mechanisms remain unclear. In this study, we found that expression levels AT-rich interaction domain-containing protein 5a (Arid5a), an RNA-binding protein, were substantially increased tumor subtypes. deletion Arid5a cell lines enhanced antitumor immunity immunocompetent mice, not immunodeficient suggesting a role for evasion. Furthermore, Arid5a-deficient microenvironment was...