@article{37f6958d49a24c4f851b852225b9757b,
title = "EDC3 phosphorylation regulates growth and invasion through controlling P-body formation and dynamics",
abstract = "Regulation of mRNA stability and translation plays a critical role in determining protein abundance within cells. Processing bodies (P-bodies) are critical regulators of these processes. Here, we report that the Pim1 and 3 protein kinases bind to the P-body protein enhancer of mRNA decapping 3 (EDC3) and phosphorylate EDC3 on serine (S)161, thereby modifying P-body assembly. EDC3 phosphorylation is highly elevated in many tumor types, is reduced upon treatment of cells with kinase inhibitors, and blocks the localization of EDC3 to P-bodies. Prostate cancer cells harboring an EDC3 S161A mutation show markedly decreased growth, migration, and invasion in tissue culture and in xenograft models. Consistent with these phenotypic changes, the expression of integrin β1 and α6 mRNA and protein is reduced in these mutated cells. These results demonstrate that EDC3 phosphorylation regulates multiple cancer-relevant functions and suggest that modulation of P-body activity may represent a new paradigm for cancer treatment.",
keywords = "P-bodies, cancers, kinases, mRNA processing, phosphorylation",
author = "Bearss, {Jeremiah J.} and Padi, {Sathish K.R.} and Neha Singh and Marina Cardo-Vila and Song, {Jin H.} and Ghassan Mouneimne and Nikita Fernandes and Yang Li and Harter, {Matthew R.} and Gard, {Jaime M.C.} and Cress, {Anne E.} and Wolfgang Peti and Nelson, {Andrew D.L.} and Buchan, {J. Ross} and Kraft, {Andrew S.} and Koichi Okumura",
note = "Funding Information: We are grateful to Dr. Michael Clarkson for his help with NMR data collection and analysis. The authors acknowledge the Experimental Mouse Shared Resource and Genome Editing Core at the University of Arizona Cancer Center (UACC) for helping with mouse experiments and CRISPR‐Cas9 editing, respectively. This work is supported by grant R01NS091336 from the National Institute of Neurological Disorders and Stroke to WP. Additionally, these experiments were supported by R21CA CA241010‐01A1 to ASK, KO, and JRB, T32 CA 9213‐40 to JB, T32 CA009213 to AEC, and NSF‐IOS 1758532 to ADLN. The cover image was created with BioRender.com. Publisher Copyright: {\textcopyright} 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
doi = "10.15252/embr.202050835",
language = "English (US)",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",
}