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Mdm2 requires Sprouty4 to regulate focal adhesion formation and metastasis independent of p53
by
Hashimoto, Naoko
, de Queiroz, Rafaela Muniz
, Efe, Gizem
, Rustgi, Anil K.
, Prives, Carol
, Tanaka, Tomoaki
, Kawashima, Yusuke
, Guzman, Asja
in
13/1
/ 13/106
/ 13/107
/ 13/109
/ 13/31
/ 13/89
/ 14/19
/ 14/5
/ 14/63
/ 38/77
/ 631/67/1798
/ 631/67/322
/ 631/80/79/2027
/ 631/80/84/2027
/ 631/80/86
/ 64/60
/ 82/29
/ 82/51
/ 82/79
/ Adhesion
/ Animals
/ Cancer
/ Cell adhesion & migration
/ Cell Cycle Proteins - genetics
/ Cell Cycle Proteins - metabolism
/ Cell Line, Tumor
/ Cell migration
/ Cell Movement - genetics
/ Cell spreading
/ Focal Adhesions - genetics
/ Focal Adhesions - metabolism
/ Gene Expression Regulation, Neoplastic
/ Humanities and Social Sciences
/ Humans
/ Invasiveness
/ MDM2 protein
/ Membrane Proteins - genetics
/ Membrane Proteins - metabolism
/ Metastases
/ Metastasis
/ Mice
/ Molecular modelling
/ multidisciplinary
/ Neoplasm Metastasis
/ Nuclear Proteins - genetics
/ Nuclear Proteins - metabolism
/ p53 Protein
/ Proto-Oncogene Proteins - genetics
/ Proto-Oncogene Proteins - metabolism
/ Proto-Oncogene Proteins c-mdm2 - genetics
/ Proto-Oncogene Proteins c-mdm2 - metabolism
/ rhoA GTP-Binding Protein - metabolism
/ RhoA protein
/ Science
/ Science (multidisciplinary)
/ Tumor suppressor genes
/ Tumor Suppressor Protein p53 - genetics
/ Tumor Suppressor Protein p53 - metabolism
/ Ubiquitin-protein ligase
2024
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Mdm2 requires Sprouty4 to regulate focal adhesion formation and metastasis independent of p53
by
Hashimoto, Naoko
, de Queiroz, Rafaela Muniz
, Efe, Gizem
, Rustgi, Anil K.
, Prives, Carol
, Tanaka, Tomoaki
, Kawashima, Yusuke
, Guzman, Asja
in
13/1
/ 13/106
/ 13/107
/ 13/109
/ 13/31
/ 13/89
/ 14/19
/ 14/5
/ 14/63
/ 38/77
/ 631/67/1798
/ 631/67/322
/ 631/80/79/2027
/ 631/80/84/2027
/ 631/80/86
/ 64/60
/ 82/29
/ 82/51
/ 82/79
/ Adhesion
/ Animals
/ Cancer
/ Cell adhesion & migration
/ Cell Cycle Proteins - genetics
/ Cell Cycle Proteins - metabolism
/ Cell Line, Tumor
/ Cell migration
/ Cell Movement - genetics
/ Cell spreading
/ Focal Adhesions - genetics
/ Focal Adhesions - metabolism
/ Gene Expression Regulation, Neoplastic
/ Humanities and Social Sciences
/ Humans
/ Invasiveness
/ MDM2 protein
/ Membrane Proteins - genetics
/ Membrane Proteins - metabolism
/ Metastases
/ Metastasis
/ Mice
/ Molecular modelling
/ multidisciplinary
/ Neoplasm Metastasis
/ Nuclear Proteins - genetics
/ Nuclear Proteins - metabolism
/ p53 Protein
/ Proto-Oncogene Proteins - genetics
/ Proto-Oncogene Proteins - metabolism
/ Proto-Oncogene Proteins c-mdm2 - genetics
/ Proto-Oncogene Proteins c-mdm2 - metabolism
/ rhoA GTP-Binding Protein - metabolism
/ RhoA protein
/ Science
/ Science (multidisciplinary)
/ Tumor suppressor genes
/ Tumor Suppressor Protein p53 - genetics
/ Tumor Suppressor Protein p53 - metabolism
/ Ubiquitin-protein ligase
2024
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Mdm2 requires Sprouty4 to regulate focal adhesion formation and metastasis independent of p53
by
Hashimoto, Naoko
, de Queiroz, Rafaela Muniz
, Efe, Gizem
, Rustgi, Anil K.
, Prives, Carol
, Tanaka, Tomoaki
, Kawashima, Yusuke
, Guzman, Asja
in
13/1
/ 13/106
/ 13/107
/ 13/109
/ 13/31
/ 13/89
/ 14/19
/ 14/5
/ 14/63
/ 38/77
/ 631/67/1798
/ 631/67/322
/ 631/80/79/2027
/ 631/80/84/2027
/ 631/80/86
/ 64/60
/ 82/29
/ 82/51
/ 82/79
/ Adhesion
/ Animals
/ Cancer
/ Cell adhesion & migration
/ Cell Cycle Proteins - genetics
/ Cell Cycle Proteins - metabolism
/ Cell Line, Tumor
/ Cell migration
/ Cell Movement - genetics
/ Cell spreading
/ Focal Adhesions - genetics
/ Focal Adhesions - metabolism
/ Gene Expression Regulation, Neoplastic
/ Humanities and Social Sciences
/ Humans
/ Invasiveness
/ MDM2 protein
/ Membrane Proteins - genetics
/ Membrane Proteins - metabolism
/ Metastases
/ Metastasis
/ Mice
/ Molecular modelling
/ multidisciplinary
/ Neoplasm Metastasis
/ Nuclear Proteins - genetics
/ Nuclear Proteins - metabolism
/ p53 Protein
/ Proto-Oncogene Proteins - genetics
/ Proto-Oncogene Proteins - metabolism
/ Proto-Oncogene Proteins c-mdm2 - genetics
/ Proto-Oncogene Proteins c-mdm2 - metabolism
/ rhoA GTP-Binding Protein - metabolism
/ RhoA protein
/ Science
/ Science (multidisciplinary)
/ Tumor suppressor genes
/ Tumor Suppressor Protein p53 - genetics
/ Tumor Suppressor Protein p53 - metabolism
/ Ubiquitin-protein ligase
2024
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Mdm2 requires Sprouty4 to regulate focal adhesion formation and metastasis independent of p53
Journal Article
Mdm2 requires Sprouty4 to regulate focal adhesion formation and metastasis independent of p53
2024
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Overview
Although the E3 ligase Mdm2 and its homologue and binding partner MdmX are the major regulators of the p53 tumor suppressor protein, it is now evident that Mdm2 and MdmX have multiple functions that do not involve p53. As one example, it is known that Mdm2 can regulate cell migration, although mechanistic insight into this function is still lacking. Here we show in cells lacking p53 expression that knockdown of Mdm2 or MdmX, as well as pharmacological inhibition of the Mdm2/MdmX complex, not only reduces cell migration and invasion, but also impairs cell spreading and focal adhesion formation. In addition, Mdm2 knockdown decreases metastasis in vivo. Interestingly, Mdm2 downregulates the expression of Sprouty4, which is required for the Mdm2 mediated effects on cell migration, focal adhesion formation and metastasis. Further, our findings indicate that Mdm2 dampening of Sprouty4 is a prerequisite for maintaining RhoA levels in the cancer cells that we have studied. Taken together we describe a molecular mechanism whereby the Mdm2/MdmX complex through Sprouty4 regulates cellular processes leading to increase metastatic capability independently of p53.
The molecular mechanism of how Mdm2 regulates cell migration remains to be elucidated. Here the authors report the role of Mdm2-x complexes, independent of p53, modulates the expression of Sprouty4 and regulates the cellular processes by decreasing the metastatic capability of cancer cells.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/106
/ 13/107
/ 13/109
/ 13/31
/ 13/89
/ 14/19
/ 14/5
/ 14/63
/ 38/77
/ 64/60
/ 82/29
/ 82/51
/ 82/79
/ Adhesion
/ Animals
/ Cancer
/ Cell Cycle Proteins - genetics
/ Cell Cycle Proteins - metabolism
/ Focal Adhesions - metabolism
/ Gene Expression Regulation, Neoplastic
/ Humanities and Social Sciences
/ Humans
/ Membrane Proteins - genetics
/ Membrane Proteins - metabolism
/ Mice
/ Nuclear Proteins - metabolism
/ Proto-Oncogene Proteins - genetics
/ Proto-Oncogene Proteins - metabolism
/ Proto-Oncogene Proteins c-mdm2 - genetics
/ Proto-Oncogene Proteins c-mdm2 - metabolism
/ rhoA GTP-Binding Protein - metabolism
/ Science
/ Tumor Suppressor Protein p53 - genetics
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