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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2023
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.
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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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