The Experts below are selected from a list of 4473 Experts worldwide ranked by ideXlab platform
Barry M Gumbiner - One of the best experts on this subject based on the ideXlab platform.
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e cadherin mediates contact inhibition of proliferation through Hippo Signaling Pathway components
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Xiao Chen, Barry M GumbinerAbstract:Contact inhibition of cell growth is essential for embryonic development and maintenance of tissue architecture in adult organisms, and the growth of tumors is characterized by a loss of contact inhibition of proliferation. The recently identified Hippo Signaling Pathway has been implicated in contact inhibition of proliferation as well as organ size control. The modulation of the phosphorylation and nuclear localization of Yes-associated protein (YAP) by the highly conserved kinase cascade of the Hippo Signaling Pathway has been intensively studied. However, cell-surface receptors regulating the Hippo Signaling Pathway in mammals are not well understood. In this study, we show that Hippo Signaling Pathway components are required for E-cadherin–dependent contact inhibition of proliferation. Knockdown of the Hippo Signaling components or overexpression of YAP inhibits the decrease in cell proliferation caused by E-cadherin homophilic binding at the cell surface, independent of other cell–cell interactions. We also demonstrate that the E-cadherin/catenin complex functions as an upstream regulator of the Hippo Signaling Pathway in mammalian cells. Expression of E-cadherin in MDA-MB-231 cells restores the density-dependent regulation of YAP nuclear exclusion. Knockdown of β-catenin in densely cultured MCF10A cells, which mainly depletes E-cadherin–bound β-catenin, induces a decrease in the phosphorylation of S127 residue of YAP and its nuclear accumulation. Moreover, E-cadherin homophilic binding independent of other cell interactions is sufficient to control the subcellular localization of YAP. Therefore, Our results indicate that, in addition to its role in cell–cell adhesion, E-cadherin-mediated cell–cell contact directly regulates the Hippo Signaling Pathway to control cell proliferation.
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e cadherin mediates contact inhibition of proliferation through Hippo Signaling Pathway components
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Xiao Chen, Barry M GumbinerAbstract:Contact inhibition of cell growth is essential for embryonic development and maintenance of tissue architecture in adult organisms, and the growth of tumors is characterized by a loss of contact inhibition of proliferation. The recently identified Hippo Signaling Pathway has been implicated in contact inhibition of proliferation as well as organ size control. The modulation of the phosphorylation and nuclear localization of Yes-associated protein (YAP) by the highly conserved kinase cascade of the Hippo Signaling Pathway has been intensively studied. However, cell-surface receptors regulating the Hippo Signaling Pathway in mammals are not well understood. In this study, we show that Hippo Signaling Pathway components are required for E-cadherin–dependent contact inhibition of proliferation. Knockdown of the Hippo Signaling components or overexpression of YAP inhibits the decrease in cell proliferation caused by E-cadherin homophilic binding at the cell surface, independent of other cell–cell interactions. We also demonstrate that the E-cadherin/catenin complex functions as an upstream regulator of the Hippo Signaling Pathway in mammalian cells. Expression of E-cadherin in MDA-MB-231 cells restores the density-dependent regulation of YAP nuclear exclusion. Knockdown of β-catenin in densely cultured MCF10A cells, which mainly depletes E-cadherin–bound β-catenin, induces a decrease in the phosphorylation of S127 residue of YAP and its nuclear accumulation. Moreover, E-cadherin homophilic binding independent of other cell interactions is sufficient to control the subcellular localization of YAP. Therefore, Our results indicate that, in addition to its role in cell–cell adhesion, E-cadherin-mediated cell–cell contact directly regulates the Hippo Signaling Pathway to control cell proliferation.
Fernando D. Camargo - One of the best experts on this subject based on the ideXlab platform.
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dynamic alterations in Hippo Signaling Pathway and yap activation during liver regeneration
American Journal of Physiology-gastrointestinal and Liver Physiology, 2014Co-Authors: James L Grijalva, Megan N Huizenga, Kaly A Mueller, Steven Rodriguez, Joseph Brazzo, Ghazaleh Sadrivakili, Fernando D. Camargo, Khashayar VakiliAbstract:The Hippo Signaling Pathway has been implicated in mammalian organ size regulation and tumor suppression. Specifically, the Hippo Pathway plays a critical role regulating the activity of transcriptional coactivator Yes-associated protein (YAP), which modulates a proliferative transcriptional program. Recent investigations have demonstrated that while this Pathway is activated in quiescent livers, its inhibition leads to liver overgrowth and tumorigenesis. However, the role of the Hippo Pathway during the natural process of liver regeneration remains unknown. Here we investigated alterations in the Hippo Signaling Pathway and YAP activation during liver regeneration using a 70% partial hepatectomy (PH) rat model. Our results indicate an increase in YAP activation by 1 day following PH as demonstrated by increased YAP nuclear localization and increased YAP target gene expression. Investigation of the Hippo Pathway revealed a decrease in the activation of core kinases Mst1/2 by 1 day as well as Lats1/2 and its adapter protein Mob1 by 3 days following PH. Evaluation of liver-to-body weight ratios indicated that the liver reaches its near normal size by 7 days following PH, which correlated with a return to baseline YAP nuclear levels and target gene expression. Additionally, when liver size was restored, Mst1/2 kinase activation returned to levels observed in quiescent livers indicating reactivation of the Hippo Signaling Pathway. These findings illustrate the dynamic changes in the Hippo Signaling Pathway and YAP activation during liver regeneration, which stabilize when the liver-to-body weight ratio reaches homeostatic levels.
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the Hippo Signaling Pathway and stem cell biology
Trends in Cell Biology, 2012Co-Authors: Azucena Ramos, Fernando D. CamargoAbstract:Stem cell (SC) activity fluctuates throughout an organism's lifetime to maintain homeostatic conditions in all tissues. As animals develop and age, their organs must remodel and regenerate themselves in response to environmental and physiological demands. Recently, the highly conserved Hippo Signaling Pathway, discovered in Drosophila melanogaster , has been implicated as a key regulator of organ size control across species. Deregulation is associated with substantial overgrowth phenotypes and eventual onset of cancer in various tissues. Importantly, emerging evidence suggests that the Hippo Pathway can modulate its effects on tissue size by the direct regulation of SC proliferation and maintenance. These findings provide an attractive model for how this Pathway might communicate physiological needs for growth to tissue-specific SC pools. In this review, we summarize the current and emerging data linking Hippo Signaling to SC function.
Xiao Chen - One of the best experts on this subject based on the ideXlab platform.
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e cadherin mediates contact inhibition of proliferation through Hippo Signaling Pathway components
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Xiao Chen, Barry M GumbinerAbstract:Contact inhibition of cell growth is essential for embryonic development and maintenance of tissue architecture in adult organisms, and the growth of tumors is characterized by a loss of contact inhibition of proliferation. The recently identified Hippo Signaling Pathway has been implicated in contact inhibition of proliferation as well as organ size control. The modulation of the phosphorylation and nuclear localization of Yes-associated protein (YAP) by the highly conserved kinase cascade of the Hippo Signaling Pathway has been intensively studied. However, cell-surface receptors regulating the Hippo Signaling Pathway in mammals are not well understood. In this study, we show that Hippo Signaling Pathway components are required for E-cadherin–dependent contact inhibition of proliferation. Knockdown of the Hippo Signaling components or overexpression of YAP inhibits the decrease in cell proliferation caused by E-cadherin homophilic binding at the cell surface, independent of other cell–cell interactions. We also demonstrate that the E-cadherin/catenin complex functions as an upstream regulator of the Hippo Signaling Pathway in mammalian cells. Expression of E-cadherin in MDA-MB-231 cells restores the density-dependent regulation of YAP nuclear exclusion. Knockdown of β-catenin in densely cultured MCF10A cells, which mainly depletes E-cadherin–bound β-catenin, induces a decrease in the phosphorylation of S127 residue of YAP and its nuclear accumulation. Moreover, E-cadherin homophilic binding independent of other cell interactions is sufficient to control the subcellular localization of YAP. Therefore, Our results indicate that, in addition to its role in cell–cell adhesion, E-cadherin-mediated cell–cell contact directly regulates the Hippo Signaling Pathway to control cell proliferation.
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e cadherin mediates contact inhibition of proliferation through Hippo Signaling Pathway components
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Xiao Chen, Barry M GumbinerAbstract:Contact inhibition of cell growth is essential for embryonic development and maintenance of tissue architecture in adult organisms, and the growth of tumors is characterized by a loss of contact inhibition of proliferation. The recently identified Hippo Signaling Pathway has been implicated in contact inhibition of proliferation as well as organ size control. The modulation of the phosphorylation and nuclear localization of Yes-associated protein (YAP) by the highly conserved kinase cascade of the Hippo Signaling Pathway has been intensively studied. However, cell-surface receptors regulating the Hippo Signaling Pathway in mammals are not well understood. In this study, we show that Hippo Signaling Pathway components are required for E-cadherin–dependent contact inhibition of proliferation. Knockdown of the Hippo Signaling components or overexpression of YAP inhibits the decrease in cell proliferation caused by E-cadherin homophilic binding at the cell surface, independent of other cell–cell interactions. We also demonstrate that the E-cadherin/catenin complex functions as an upstream regulator of the Hippo Signaling Pathway in mammalian cells. Expression of E-cadherin in MDA-MB-231 cells restores the density-dependent regulation of YAP nuclear exclusion. Knockdown of β-catenin in densely cultured MCF10A cells, which mainly depletes E-cadherin–bound β-catenin, induces a decrease in the phosphorylation of S127 residue of YAP and its nuclear accumulation. Moreover, E-cadherin homophilic binding independent of other cell interactions is sufficient to control the subcellular localization of YAP. Therefore, Our results indicate that, in addition to its role in cell–cell adhesion, E-cadherin-mediated cell–cell contact directly regulates the Hippo Signaling Pathway to control cell proliferation.
Narumi Ogonuki - One of the best experts on this subject based on the ideXlab platform.
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the Hippo Signaling Pathway components lats and yap pattern tead4 activity to distinguish mouse trophectoderm from inner cell mass
Developmental Cell, 2009Co-Authors: Noriyuki Nishioka, Kenichi Inoue, Kenjiro Adachi, Hiroshi Kiyonari, Amy Ralston, Norikazu Yabuta, Shino Hirahara, Robert O Stephenson, Narumi Ogonuki, Ryosuke MakitaAbstract:Outside cells of the preimplantation mouse embryo form the trophectoderm (TE), a process requiring the transcription factor Tead4. Here, we show that transcriptionally active Tead4 can induce Cdx2 and other trophoblast genes in parallel in embryonic stem cells. In embryos, the Tead4 coactivator protein Yap localizes to nuclei of outside cells, and modulation of Tead4 or Yap activity leads to changes in Cdx2 expression. In inside cells, Yap is phosphorylated and cytoplasmic, and this involves the Hippo Signaling Pathway component Lats. We propose that active Tead4 promotes TE development in outside cells, whereas Tead4 activity is suppressed in inside cells by cell contact- and Lats-mediated inhibition of nuclear Yap localization. Thus, differential Signaling between inside and outside cell populations leads to changes in cell fate specification during TE formation.
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the Hippo Signaling Pathway components lats and yap pattern tead4 activity to distinguish mouse trophectoderm from inner cell mass
Developmental Cell, 2009Co-Authors: Noriyuki Nishioka, Kenichi Inoue, Kenjiro Adachi, Hiroshi Kiyonari, Amy Ralston, Norikazu Yabuta, Shino Hirahara, Robert O Stephenson, Mitsunori Ota, Narumi OgonukiAbstract:Outside cells of the preimplantation mouse embryo form the trophectoderm (TE), a process requiring the transcription factor Tead4. Here, we show that transcriptionally active Tead4 can induce Cdx2 and other trophoblast genes in parallel in embryonic stem cells. In embryos, the Tead4 coactivator protein Yap localizes to nuclei of outside cells, and modulation of Tead4 or Yap activity leads to changes in Cdx2 expression. In inside cells, Yap is phosphorylated and cytoplasmic, and this involves the Hippo Signaling Pathway component Lats. We propose that active Tead4 promotes TE development in outside cells, whereas Tead4 activity is suppressed in inside cells by cell contact- and Lats-mediated inhibition of nuclear Yap localization. Thus, differential Signaling between inside and outside cell populations leads to changes in cell fate specification during TE formation.
Noriyuki Nishioka - One of the best experts on this subject based on the ideXlab platform.
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the Hippo Signaling Pathway components lats and yap pattern tead4 activity to distinguish mouse trophectoderm from inner cell mass
Developmental Cell, 2009Co-Authors: Noriyuki Nishioka, Kenichi Inoue, Kenjiro Adachi, Hiroshi Kiyonari, Amy Ralston, Norikazu Yabuta, Shino Hirahara, Robert O Stephenson, Narumi Ogonuki, Ryosuke MakitaAbstract:Outside cells of the preimplantation mouse embryo form the trophectoderm (TE), a process requiring the transcription factor Tead4. Here, we show that transcriptionally active Tead4 can induce Cdx2 and other trophoblast genes in parallel in embryonic stem cells. In embryos, the Tead4 coactivator protein Yap localizes to nuclei of outside cells, and modulation of Tead4 or Yap activity leads to changes in Cdx2 expression. In inside cells, Yap is phosphorylated and cytoplasmic, and this involves the Hippo Signaling Pathway component Lats. We propose that active Tead4 promotes TE development in outside cells, whereas Tead4 activity is suppressed in inside cells by cell contact- and Lats-mediated inhibition of nuclear Yap localization. Thus, differential Signaling between inside and outside cell populations leads to changes in cell fate specification during TE formation.
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the Hippo Signaling Pathway components lats and yap pattern tead4 activity to distinguish mouse trophectoderm from inner cell mass
Developmental Cell, 2009Co-Authors: Noriyuki Nishioka, Kenichi Inoue, Kenjiro Adachi, Hiroshi Kiyonari, Amy Ralston, Norikazu Yabuta, Shino Hirahara, Robert O Stephenson, Mitsunori Ota, Narumi OgonukiAbstract:Outside cells of the preimplantation mouse embryo form the trophectoderm (TE), a process requiring the transcription factor Tead4. Here, we show that transcriptionally active Tead4 can induce Cdx2 and other trophoblast genes in parallel in embryonic stem cells. In embryos, the Tead4 coactivator protein Yap localizes to nuclei of outside cells, and modulation of Tead4 or Yap activity leads to changes in Cdx2 expression. In inside cells, Yap is phosphorylated and cytoplasmic, and this involves the Hippo Signaling Pathway component Lats. We propose that active Tead4 promotes TE development in outside cells, whereas Tead4 activity is suppressed in inside cells by cell contact- and Lats-mediated inhibition of nuclear Yap localization. Thus, differential Signaling between inside and outside cell populations leads to changes in cell fate specification during TE formation.