@article{8c9b31a941a24a5a855c8ab9977b1bc8,
title = "PIM1 phosphorylates ABI2 to enhance actin dynamics and promote tumor invasion",
abstract = "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.",
author = "Jensen, {Corbin C.} and Clements, {Amber N.} and Hope Liou and Ball, {Lauren E.} and Bethard, {Jennifer R.} and Langlais, {Paul R.} and Toth, {Rachel K.} and Chauhan, {Shailender S.} and Casillas, {Andrea L.} and Daulat, {Sohail R.} and Kraft, {Andrew S.} and Cress, {Anne E.} and Miranti, {Cindy K.} and Ghassan Mouneimne and Rogers, {Greg C.} and Warfel, {Noel A.}",
note = "Funding Information: We would like to thank the following shared resources at the University of Arizona Cancer Center for their help and support: EMSR, TACMASR, and Biostatistics. We would also like to thank Dr. Andrew Paek for his help with MATLAB coding. Studies were supported by funding from the Department of Defense Prostate Cancer Research Program (W81XWH-19-10455) to N.A. Warfel, and the National Cancer Institute (F31CA254256-01A1 and T32CA009213-41A1) to C.C. Jensen. A Cancer Center Support grant from the National Institute of Health (P30CA023074) also supported this research. Open Access funding provided by the University of Arizona. Funding Information: Studies were supported by funding from the Department of Defense Prostate Cancer Research Program (W81XWH-19-1-0455) to N.A. Warfel, and the National Cancer Institute (F31CA254256-01A1 and T32CA009213-41A1) to C.C. Jensen. A Cancer Center Support grant from the National Institute of Health (P30CA023074) also supported this research. Open Access funding provided by the University of Arizona. Publisher Copyright: {\textcopyright} 2023 Jensen et al.",
year = "2023",
month = jun,
day = "5",
doi = "10.1083/jcb.202208136",
language = "English (US)",
volume = "222",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "6",
}