Small molecule inhibition of Dynamin-dependent endocytosis targets multiple niche signals and impairs leukemia stem cells

Cedric S. Tremblay; Sung Kai Chiu; Jesslyn Saw; Hannah McCalmont; Veronique Litalien; Jacqueline Boyle; Stefan E. Sonderegger; Ngoc Chau; Kathryn Evans; Loretta Cerruti; Jessica M. Salmon; Adam McCluskey; Richard B. Lock; Phillip J. Robinson; Stephen M. Jane; David J. Curtis

doi:10.1038/s41467-020-20091-6

Nature Communications (Dec 2020)

Small molecule inhibition of Dynamin-dependent endocytosis targets multiple niche signals and impairs leukemia stem cells

Cedric S. Tremblay,
Sung Kai Chiu,
Jesslyn Saw,
Hannah McCalmont,
Veronique Litalien,
Jacqueline Boyle,
Stefan E. Sonderegger,
Ngoc Chau,
Kathryn Evans,
Loretta Cerruti,
Jessica M. Salmon,
Adam McCluskey,
Richard B. Lock,
Phillip J. Robinson,
Stephen M. Jane,
David J. Curtis

Affiliations

Cedric S. Tremblay: Australian Centre for Blood Diseases, Central Clinical School, Monash University
Sung Kai Chiu: Australian Centre for Blood Diseases, Central Clinical School, Monash University
Jesslyn Saw: Australian Centre for Blood Diseases, Central Clinical School, Monash University
Hannah McCalmont: Lowy Cancer Research Centre, Children’s Cancer Institute, University of New South Wales
Veronique Litalien: Australian Centre for Blood Diseases, Central Clinical School, Monash University
Jacqueline Boyle: Australian Centre for Blood Diseases, Central Clinical School, Monash University
Stefan E. Sonderegger: Australian Centre for Blood Diseases, Central Clinical School, Monash University
Ngoc Chau: Cell Signalling Unit, Children’s Medical Research Institute
Kathryn Evans: Lowy Cancer Research Centre, Children’s Cancer Institute, University of New South Wales
Loretta Cerruti: Australian Centre for Blood Diseases, Central Clinical School, Monash University
Jessica M. Salmon: Australian Centre for Blood Diseases, Central Clinical School, Monash University
Adam McCluskey: Chemistry, Centre for Chemical Biology, School of Environmental and Life Sciences, University of Newcastle
Richard B. Lock: Lowy Cancer Research Centre, Children’s Cancer Institute, University of New South Wales
Phillip J. Robinson: Cell Signalling Unit, Children’s Medical Research Institute
Stephen M. Jane: Australian Centre for Blood Diseases, Central Clinical School, Monash University
David J. Curtis: Australian Centre for Blood Diseases, Central Clinical School, Monash University

DOI: https://doi.org/10.1038/s41467-020-20091-6
Journal volume & issue: Vol. 11, no. 1
pp. 1 – 18

Abstract

Read online

The tumour microenvironment provides signals to support leukaemic stem cells (LSC) maintenance and chemoresistance. Here, the authors show that disrupting niche-associated signalling by inhibiting receptor-mediated endocytosis with a dynamin GTPase inhibitor overcomes chemoresistance of LSC.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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