TY - JOUR
T1 - Targeting the actin nucleation promoting factor WASp provides a therapeutic approach for hematopoietic malignancies
AU - Biber, Guy
AU - Ben-Shmuel, Aviad
AU - Noy, Elad
AU - Joseph, Noah
AU - Puthenveetil, Abhishek
AU - Reiss, Neria
AU - Levy, Omer
AU - Lazar, Itay
AU - Feiglin, Ariel
AU - Ofran, Yanay
AU - Kedmi, Meirav
AU - Avigdor, Abraham
AU - Fried, Sophia
AU - Barda-Saad, Mira
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85115411341&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-25842-7
DO - 10.1038/s41467-021-25842-7
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C2 - 34552085
AN - SCOPUS:85115411341
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5581
ER -
