PTU, a novel ureido-fatty acid, inhibits MDA-MB-231 cell invasion and dissemination by modulating Wnt5a secretion and cytoskeletal signaling.
Full text not available from this repository.Item Type: | Article |
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Status: | Published |
Official URL: | https://doi.org/10.1016/j.bcp.2021.114726 |
Journal or Publication Title: | Biochemical Pharmacology |
Volume: | 192 |
Page Range: | p. 114726 |
Date: | October 2021 |
Divisions: | Lipid Cell Biology |
Depositing User: | General Admin |
Identification Number: | 10.1016/j.bcp.2021.114726 |
ISSN: | 00062952 |
Date Deposited: | 06 Oct 2021 05:16 |
Abstract: | Migration and invasion promote tumor cell metastasis, which is the leading cause of cancer death. At present there are no effective treatments. Epidemiological studies have suggested that ω-3 polyunsaturated fatty acids (PUFA) may decrease cancer aggressiveness. In recent studies epoxide metabolites of ω-3 PUFA exhibited anti-cancer activity, although increased in vivo stability is required to develop useful drugs. Here we synthesized novel stabilized ureido-fatty acid ω-3 epoxide isosteres and found that one analogue - p-tolyl-ureidopalmitic acid (PTU) - inhibited migration and invasion by MDA-MB-231 breast cancer cells in vitro and in vivo in xenografted nu/nu mice. From proteomics analysis of PTU-treated cells major regulated pathways were linked to the actin cytoskeleton and actin-based motility. The principal finding was that PTU impaired the formation of actin protrusions by decreasing the secretion of Wnt5a, which dysregulated the Wnt/planar cell polarity (PCP) pathway and actin cytoskeletal dynamics. Exogenous Wnt5a restored invasion and Wnt/PCP signalling in PTU-treated cells. PTU is the prototype of a novel class of agents that selectively dysregulate the Wnt/PCP pathway by inhibiting Wnt5a secretion and actin dynamics to impair MDA-MB-231 cell migration and invasion. Keywords: Actin cytoskeleton; Cancer cell migration; Wnt5a; ω-3 fatty acid epoxide isosteres. Copyright © 2021 Elsevier Inc. All rights reserved. |
Creators: | Creators Email al-Zubaidi, Yassir UNSPECIFIED Chen, Yongjuan UNSPECIFIED Khalilur Rahman, Md. UNSPECIFIED Umashankar, Bala UNSPECIFIED Choucair, Hassan UNSPECIFIED Bourget, Kirsi UNSPECIFIED Chung, Long UNSPECIFIED Qi, Yanfei UNSPECIFIED Witting, Paul K. UNSPECIFIED Anderson, Robin L. UNSPECIFIED O'Neill, Geraldine M. UNSPECIFIED Dunstan, Colin R. UNSPECIFIED Rawling, Tristan UNSPECIFIED Murray, Michael UNSPECIFIED |
Last Modified: | 06 Oct 2021 05:16 |
URI: | https://eprints.centenary.org.au/id/eprint/1140 |
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