The Experts below are selected from a list of 2445 Experts worldwide ranked by ideXlab platform
Hao Zhou - One of the best experts on this subject based on the ideXlab platform.
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yap promotes hepatocellular carcinoma metastasis and mobilization via governing cofilin f actin Lamellipodium axis by regulation of jnk bnip3 serca camkii pathways
Redox biology, 2018Co-Authors: Chen Shi, Yong Cai, Pingjun Zhu, Weihu Wang, Hao ZhouAbstract:Despite the increasingly important role of Hippo-Yap in hepatocellular carcinoma (HCC) development and progression, little insight is available at the time regarding the specifics interaction of Yap and cancer cells migration. Here, we identified the mechanism by which tumor-intrinsic Yap deletion resulted in HCC migratory inhibition. Yap was greatly upregulated in HCC and its expression promoted the cells migration. Functional studies found that knockdown of Yap induced JNK phosphorylation which closely bound to the Bnip3 promoter and contributed to Bnip3 expression. Higher Bnip3 employed excessive mitophagy leading to mitochondrial dysfunction and ATP shortage. The insufficient ATP inactivated SERCA and consequently triggered intracellular calcium overload. As the consequence of calcium oscillation, Ca/calmodulin-dependent protein kinases II (CaMKII) was signaled and subsequently inhibited cofilin activity via phosphorylated modification. The phosphorylated cofilin failed to manipulate F-actin polymerization and Lamellipodium formation, resulting into the impairment of Lamellipodium-based migration. Collectively, our results identified Hippo-Yap as the tumor promoter in hepatocellular carcinoma that mediated via activation of cofilin/F-actin/Lamellipodium axis by limiting JNK-Bnip3-SERCA-CaMKII pathways, with potential application to HCC therapy involving cancer metastasis.
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Yap promotes hepatocellular carcinoma metastasis and mobilization via governing cofilin/F-actin/Lamellipodium axis by regulation of JNK/Bnip3/SERCA/CaMKII pathways
Elsevier, 2018Co-Authors: Chen Shi, Yong Cai, Pingjun Zhu, Weihu Wang, Hao ZhouAbstract:Despite the increasingly important role of Hippo-Yap in hepatocellular carcinoma (HCC) development and progression, little insight is available at the time regarding the specifics interaction of Yap and cancer cells migration. Here, we identified the mechanism by which tumor-intrinsic Yap deletion resulted in HCC migratory inhibition. Yap was greatly upregulated in HCC and its expression promoted the cells migration. Functional studies found that knockdown of Yap induced JNK phosphorylation which closely bound to the Bnip3 promoter and contributed to Bnip3 expression. Higher Bnip3 employed excessive mitophagy leading to mitochondrial dysfunction and ATP shortage. The insufficient ATP inactivated SERCA and consequently triggered intracellular calcium overload. As the consequence of calcium oscillation, Ca/calmodulin-dependent protein kinases II (CaMKII) was signaled and subsequently inhibited cofilin activity via phosphorylated modification. The phosphorylated cofilin failed to manipulate F-actin polymerization and Lamellipodium formation, resulting into the impairment of Lamellipodium-based migration. Collectively, our results identified Hippo-Yap as the tumor promoter in hepatocellular carcinoma that mediated via activation of cofilin/F-actin/Lamellipodium axis by limiting JNK-Bnip3-SERCA-CaMKII pathways, with potential application to HCC therapy involving cancer metastasis. Keywords: Yap, JNK, Bnip3, SERCA, CaMKII, F-actin, Cofilin, Lamellipodium, Migratio
Alan Rick Horwitz - One of the best experts on this subject based on the ideXlab platform.
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actin and alpha actinin orchestrate the assembly and maturation of nascent adhesions in a myosin ii motor independent manner
Nature Cell Biology, 2008Co-Authors: Colin K Choi, Miguel Vicentemanzanares, Jessica Zareno, Leanna Whitmore, Alex Mogilner, Alan Rick HorwitzAbstract:Adhesion assembly is needed for cell migration. Horwitz and colleagues report that new adhesions assemble in the Lamellipodium in a manner that is independent of myosin II but requires actin polymerization.
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actin and alpha actinin orchestrate the assembly and maturation of nascent adhesions in a myosin ii motor independent manner
Nature Cell Biology, 2008Co-Authors: Colin K Choi, Miguel Vicentemanzanares, Jessica Zareno, Leanna Whitmore, Alex Mogilner, Alan Rick HorwitzAbstract:Using two-colour imaging and high resolution TIRF microscopy, we investigated the assembly and maturation of nascent adhesions in migrating cells. We show that nascent adhesions assemble and are stable within the Lamellipodium. The assembly is independent of myosin II but its rate is proportional to the protrusion rate and requires actin polymerization. At the Lamellipodium back, the nascent adhesions either disassemble or mature through growth and elongation. Maturation occurs along an alpha-actinin-actin template that elongates centripetally from nascent adhesions. Alpha-Actinin mediates the formation of the template and organization of adhesions associated with actin filaments, suggesting that actin crosslinking has a major role in this process. Adhesion maturation also requires myosin II. Rescue of a myosin IIA knockdown with an actin-bound but motor-inhibited mutant of myosin IIA shows that the actin crosslinking function of myosin II mediates initial adhesion maturation. From these studies, we have developed a model for adhesion assembly that clarifies the relative contributions of myosin II and actin polymerization and organization.
Mark H Ginsberg - One of the best experts on this subject based on the ideXlab platform.
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an α 4 integrin paxillin arf gap complex restricts rac activation to the leading edge of migrating cells
Nature Cell Biology, 2005Co-Authors: Naoyuki Nishiya, William B Kiosses, Jaewon Han, Mark H GinsbergAbstract:Formation of a stable Lamellipodium at the front of migrating cells requires localization of Rac activation to the leading edge. Restriction of alpha4 integrin phosphorylation to the leading edge limits the interaction of alpha4 with paxillin to the sides and rear of a migrating cell. The alpha4-paxillin complex inhibits stable lamellipodia, thus confining lamellipod formation to the cell anterior. Here we report that binding of paxillin to the alpha4 integrin subunit inhibits adhesion-dependent Lamellipodium formation by blocking Rac activation. The paxillin LD4 domain mediates this reduction in Rac activity by recruiting an ADP-ribosylation factor GTPase-activating protein (Arf-GAP) that decreases Arf activity, thereby inhibiting Rac. Finally, the localized formation of the alpha4-paxillin-Arf-GAP complex mediates the polarization of Rac activity and promotes directional cell migration. These findings establish a mechanism for the spatial localization of Rac activity to enhance cell migration.
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an alpha4 integrin paxillin arf gap complex restricts rac activation to the leading edge of migrating cells
Nature Cell Biology, 2005Co-Authors: Naoyuki Nishiya, William B Kiosses, Jaewon Han, Mark H GinsbergAbstract:Formation of a stable Lamellipodium at the front of migrating cells requires localization of Rac activation to the leading edge. Restriction of alpha4 integrin phosphorylation to the leading edge limits the interaction of alpha4 with paxillin to the sides and rear of a migrating cell. The alpha4-paxillin complex inhibits stable lamellipodia, thus confining lamellipod formation to the cell anterior. Here we report that binding of paxillin to the alpha4 integrin subunit inhibits adhesion-dependent Lamellipodium formation by blocking Rac activation. The paxillin LD4 domain mediates this reduction in Rac activity by recruiting an ADP-ribosylation factor GTPase-activating protein (Arf-GAP) that decreases Arf activity, thereby inhibiting Rac. Finally, the localized formation of the alpha4-paxillin-Arf-GAP complex mediates the polarization of Rac activity and promotes directional cell migration. These findings establish a mechanism for the spatial localization of Rac activity to enhance cell migration.
Colin K Choi - One of the best experts on this subject based on the ideXlab platform.
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actin and alpha actinin orchestrate the assembly and maturation of nascent adhesions in a myosin ii motor independent manner
Nature Cell Biology, 2008Co-Authors: Colin K Choi, Miguel Vicentemanzanares, Jessica Zareno, Leanna Whitmore, Alex Mogilner, Alan Rick HorwitzAbstract:Adhesion assembly is needed for cell migration. Horwitz and colleagues report that new adhesions assemble in the Lamellipodium in a manner that is independent of myosin II but requires actin polymerization.
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actin and alpha actinin orchestrate the assembly and maturation of nascent adhesions in a myosin ii motor independent manner
Nature Cell Biology, 2008Co-Authors: Colin K Choi, Miguel Vicentemanzanares, Jessica Zareno, Leanna Whitmore, Alex Mogilner, Alan Rick HorwitzAbstract:Using two-colour imaging and high resolution TIRF microscopy, we investigated the assembly and maturation of nascent adhesions in migrating cells. We show that nascent adhesions assemble and are stable within the Lamellipodium. The assembly is independent of myosin II but its rate is proportional to the protrusion rate and requires actin polymerization. At the Lamellipodium back, the nascent adhesions either disassemble or mature through growth and elongation. Maturation occurs along an alpha-actinin-actin template that elongates centripetally from nascent adhesions. Alpha-Actinin mediates the formation of the template and organization of adhesions associated with actin filaments, suggesting that actin crosslinking has a major role in this process. Adhesion maturation also requires myosin II. Rescue of a myosin IIA knockdown with an actin-bound but motor-inhibited mutant of myosin IIA shows that the actin crosslinking function of myosin II mediates initial adhesion maturation. From these studies, we have developed a model for adhesion assembly that clarifies the relative contributions of myosin II and actin polymerization and organization.
Chen Shi - One of the best experts on this subject based on the ideXlab platform.
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yap promotes hepatocellular carcinoma metastasis and mobilization via governing cofilin f actin Lamellipodium axis by regulation of jnk bnip3 serca camkii pathways
Redox biology, 2018Co-Authors: Chen Shi, Yong Cai, Pingjun Zhu, Weihu Wang, Hao ZhouAbstract:Despite the increasingly important role of Hippo-Yap in hepatocellular carcinoma (HCC) development and progression, little insight is available at the time regarding the specifics interaction of Yap and cancer cells migration. Here, we identified the mechanism by which tumor-intrinsic Yap deletion resulted in HCC migratory inhibition. Yap was greatly upregulated in HCC and its expression promoted the cells migration. Functional studies found that knockdown of Yap induced JNK phosphorylation which closely bound to the Bnip3 promoter and contributed to Bnip3 expression. Higher Bnip3 employed excessive mitophagy leading to mitochondrial dysfunction and ATP shortage. The insufficient ATP inactivated SERCA and consequently triggered intracellular calcium overload. As the consequence of calcium oscillation, Ca/calmodulin-dependent protein kinases II (CaMKII) was signaled and subsequently inhibited cofilin activity via phosphorylated modification. The phosphorylated cofilin failed to manipulate F-actin polymerization and Lamellipodium formation, resulting into the impairment of Lamellipodium-based migration. Collectively, our results identified Hippo-Yap as the tumor promoter in hepatocellular carcinoma that mediated via activation of cofilin/F-actin/Lamellipodium axis by limiting JNK-Bnip3-SERCA-CaMKII pathways, with potential application to HCC therapy involving cancer metastasis.
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Yap promotes hepatocellular carcinoma metastasis and mobilization via governing cofilin/F-actin/Lamellipodium axis by regulation of JNK/Bnip3/SERCA/CaMKII pathways
Elsevier, 2018Co-Authors: Chen Shi, Yong Cai, Pingjun Zhu, Weihu Wang, Hao ZhouAbstract:Despite the increasingly important role of Hippo-Yap in hepatocellular carcinoma (HCC) development and progression, little insight is available at the time regarding the specifics interaction of Yap and cancer cells migration. Here, we identified the mechanism by which tumor-intrinsic Yap deletion resulted in HCC migratory inhibition. Yap was greatly upregulated in HCC and its expression promoted the cells migration. Functional studies found that knockdown of Yap induced JNK phosphorylation which closely bound to the Bnip3 promoter and contributed to Bnip3 expression. Higher Bnip3 employed excessive mitophagy leading to mitochondrial dysfunction and ATP shortage. The insufficient ATP inactivated SERCA and consequently triggered intracellular calcium overload. As the consequence of calcium oscillation, Ca/calmodulin-dependent protein kinases II (CaMKII) was signaled and subsequently inhibited cofilin activity via phosphorylated modification. The phosphorylated cofilin failed to manipulate F-actin polymerization and Lamellipodium formation, resulting into the impairment of Lamellipodium-based migration. Collectively, our results identified Hippo-Yap as the tumor promoter in hepatocellular carcinoma that mediated via activation of cofilin/F-actin/Lamellipodium axis by limiting JNK-Bnip3-SERCA-CaMKII pathways, with potential application to HCC therapy involving cancer metastasis. Keywords: Yap, JNK, Bnip3, SERCA, CaMKII, F-actin, Cofilin, Lamellipodium, Migratio
