Neurokinin-1 receptor is an effective target for treating leukemia by inducing oxidative stress through mitochondrial calcium overload

C Ge; H Huang; F Huang; T Yang; T Zhang; H Wu; H Zhou; Q Chen; Y Shi; Y Sun; L Liu; X Wang; RB Pearson; Y Cao; J Kang; C Fu

Journal article

Neurokinin-1 receptor is an effective target for treating leukemia by inducing oxidative stress through mitochondrial calcium overload

C Ge, H Huang, F Huang, T Yang, T Zhang, H Wu, H Zhou, Q Chen, Y Shi, Y Sun, L Liu, X Wang, RB Pearson, Y Cao, J Kang, C Fu

Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2019

DOI: 10.1073/pnas.1908998116

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Abstract

Substance P (SP) regulates multiple biological processes through its high-affinity neurokinin-1 receptor (NK-1R). While the SP/NK-1R signaling axis is involved in the pathogenesis of solid cancer, the role of this signaling pathway in hematological malignancy remains unknown. Here, we demonstrate that NK-1R expression is markedly elevated in the white blood cells from acute myeloid leukemia patients and a panel of human leukemia cell lines. Blocking NK-1R induces apoptosis in vitro and in vivo via increase of mitochondrial reactive oxygen species. This oxidative stress was triggered by rapid calcium flux from the endoplasmic reticulum into mitochondria and, consequently, impairment of mitoch..

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University of Melbourne Researchers

Richard Pearson Author

Jian Kang Author

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ONCOGENIC SIGNALING AND CANCER THERAPY

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Grants

Awarded by National Health and Medical Research Council

Funding Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grants 81770176 and 31470071), the Zhejiang Provincial Nature Science Foundation of China (Grant LY14C050003), the New Century 151 Talent Project of Zhejiang Province, the 521 Talent Foundation and the Fundamental Research Funds of Zhejiang Sci-Tech University (Grant 2019Y001), the Open Foundation from the Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province (Grant ZJZLSYS004), and a Senior Research Fellowship (1058586) and Program Grant (1053792) to R.B.P. from the National Health and Medical Research Council (NHMRC) of Australia.