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PIM1 phosphorylates ABI2 to enhance actin dynamics and promote tumor invasion
Distinguishing key factors that drive the switch from indolent to invasive disease will make a significant impact on guiding the treatment of prostate cancer (PCa) patients. Here, we identify a novel signaling pathway linking hypoxia and PIM1 kinase to the actin cytoskeleton and cell motility. An un...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10103708/ https://www.ncbi.nlm.nih.gov/pubmed/37042842 http://dx.doi.org/10.1083/jcb.202208136 |
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author | Jensen, Corbin C. Clements, Amber N. Liou, Hope Ball, Lauren E. Bethard, Jennifer R. Langlais, Paul R. Toth, Rachel K. Chauhan, Shailender S. Casillas, Andrea L. Daulat, Sohail R. Kraft, Andrew S. Cress, Anne E. Miranti, Cindy K. Mouneimne, Ghassan Rogers, Greg C. Warfel, Noel A. |
author_facet | Jensen, Corbin C. Clements, Amber N. Liou, Hope Ball, Lauren E. Bethard, Jennifer R. Langlais, Paul R. Toth, Rachel K. Chauhan, Shailender S. Casillas, Andrea L. Daulat, Sohail R. Kraft, Andrew S. Cress, Anne E. Miranti, Cindy K. Mouneimne, Ghassan Rogers, Greg C. Warfel, Noel A. |
author_sort | Jensen, Corbin C. |
collection | PubMed |
description | Distinguishing key factors that drive the switch from indolent to invasive disease will make a significant impact on guiding the treatment of prostate cancer (PCa) patients. Here, we identify a novel signaling pathway linking hypoxia and PIM1 kinase to the actin cytoskeleton and cell motility. An unbiased proteomic screen identified Abl-interactor 2 (ABI2), an integral member of the wave regulatory complex (WRC), as a PIM1 substrate. Phosphorylation of ABI2 at Ser183 by PIM1 increased ABI2 protein levels and enhanced WRC formation, resulting in increased protrusive activity and cell motility. Cell protrusion induced by hypoxia and/or PIM1 was dependent on ABI2. In vivo smooth muscle invasion assays showed that overexpression of PIM1 significantly increased the depth of tumor cell invasion, and treatment with PIM inhibitors significantly reduced intramuscular PCa invasion. This research uncovers a HIF-1-independent signaling axis that is critical for hypoxia-induced invasion and establishes a novel role for PIM1 as a key regulator of the actin cytoskeleton. |
format | Online Article Text |
id | pubmed-10103708 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-101037082023-04-15 PIM1 phosphorylates ABI2 to enhance actin dynamics and promote tumor invasion Jensen, Corbin C. Clements, Amber N. Liou, Hope Ball, Lauren E. Bethard, Jennifer R. Langlais, Paul R. Toth, Rachel K. Chauhan, Shailender S. Casillas, Andrea L. Daulat, Sohail R. Kraft, Andrew S. Cress, Anne E. Miranti, Cindy K. Mouneimne, Ghassan Rogers, Greg C. Warfel, Noel A. J Cell Biol Article Distinguishing key factors that drive the switch from indolent to invasive disease will make a significant impact on guiding the treatment of prostate cancer (PCa) patients. Here, we identify a novel signaling pathway linking hypoxia and PIM1 kinase to the actin cytoskeleton and cell motility. An unbiased proteomic screen identified Abl-interactor 2 (ABI2), an integral member of the wave regulatory complex (WRC), as a PIM1 substrate. Phosphorylation of ABI2 at Ser183 by PIM1 increased ABI2 protein levels and enhanced WRC formation, resulting in increased protrusive activity and cell motility. Cell protrusion induced by hypoxia and/or PIM1 was dependent on ABI2. In vivo smooth muscle invasion assays showed that overexpression of PIM1 significantly increased the depth of tumor cell invasion, and treatment with PIM inhibitors significantly reduced intramuscular PCa invasion. This research uncovers a HIF-1-independent signaling axis that is critical for hypoxia-induced invasion and establishes a novel role for PIM1 as a key regulator of the actin cytoskeleton. Rockefeller University Press 2023-04-12 /pmc/articles/PMC10103708/ /pubmed/37042842 http://dx.doi.org/10.1083/jcb.202208136 Text en © 2023 Jensen et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jensen, Corbin C. Clements, Amber N. Liou, Hope Ball, Lauren E. Bethard, Jennifer R. Langlais, Paul R. Toth, Rachel K. Chauhan, Shailender S. Casillas, Andrea L. Daulat, Sohail R. Kraft, Andrew S. Cress, Anne E. Miranti, Cindy K. Mouneimne, Ghassan Rogers, Greg C. Warfel, Noel A. PIM1 phosphorylates ABI2 to enhance actin dynamics and promote tumor invasion |
title | PIM1 phosphorylates ABI2 to enhance actin dynamics and promote tumor invasion |
title_full | PIM1 phosphorylates ABI2 to enhance actin dynamics and promote tumor invasion |
title_fullStr | PIM1 phosphorylates ABI2 to enhance actin dynamics and promote tumor invasion |
title_full_unstemmed | PIM1 phosphorylates ABI2 to enhance actin dynamics and promote tumor invasion |
title_short | PIM1 phosphorylates ABI2 to enhance actin dynamics and promote tumor invasion |
title_sort | pim1 phosphorylates abi2 to enhance actin dynamics and promote tumor invasion |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10103708/ https://www.ncbi.nlm.nih.gov/pubmed/37042842 http://dx.doi.org/10.1083/jcb.202208136 |
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