Targeting the actin nucleation promoting factor WASp provides a therapeutic approach for hematopoietic malignancies

Guy Biber, Aviad Ben-Shmuel, Elad Noy, Noah Joseph, Abhishek Puthenveetil, Neria Reiss, Omer Levy, Itay Lazar, Ariel Feiglin, Yanay Ofran, Meirav Kedmi, Abraham Avigdor, Sophia Fried and Mira Barda-Saad ()
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Guy Biber: Bar-Ilan University
Aviad Ben-Shmuel: Bar-Ilan University
Elad Noy: Bar-Ilan University
Noah Joseph: Bar-Ilan University
Abhishek Puthenveetil: Bar-Ilan University
Neria Reiss: Bar-Ilan University
Omer Levy: Bar-Ilan University
Itay Lazar: Bar-Ilan University
Ariel Feiglin: Bar-Ilan University
Yanay Ofran: Bar-Ilan University
Meirav Kedmi: Bar-Ilan University
Abraham Avigdor: Chaim Sheba Medical Center
Sophia Fried: Bar-Ilan University
Mira Barda-Saad: Bar-Ilan University

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: Abstract Cancer cells depend on actin cytoskeleton rearrangement to carry out hallmark malignant functions including activation, proliferation, migration and invasiveness. Wiskott–Aldrich Syndrome protein (WASp) is an actin nucleation-promoting factor and is a key regulator of actin polymerization in hematopoietic cells. The involvement of WASp in malignancies is incompletely understood. Since WASp is exclusively expressed in hematopoietic cells, we performed in silico screening to identify small molecule compounds (SMCs) that bind WASp and promote its degradation. We describe here one such identified molecule; this WASp-targeting SMC inhibits key WASp-dependent actin processes in several types of hematopoietic malignancies in vitro and in vivo without affecting naïve healthy cells. This small molecule demonstrates limited toxicity and immunogenic effects, and thus, might serve as an effective strategy to treat specific hematopoietic malignancies in a safe and precisely targeted manner.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25842-7

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DOI: 10.1038/s41467-021-25842-7

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