Daptomycin suppresses tumor migration and angiogenesis via binding to ribosomal protein S19 in humans

Sung Min Cho; Hwa Jung Lee; Peter Karuso; Ho Jeong Kwon

doi:10.1038/s41429-021-00446-x

Daptomycin suppresses tumor migration and angiogenesis via binding to ribosomal protein S19 in humans

Sung Min Cho, Hwa Jung Lee, Peter Karuso, Ho Jeong Kwon

Research output: Contribution to journal › Article › peer-review

Abstract

We have previously reported that daptomycin (DAP), a last resort antibiotic, binds to ribosomal protein S19 (RPS19) in humans and exhibits selective anti-cancer activity against MCF7 breast cancer cells. Here, we investigated the role of RPS19 in the anti-cancer effects of DAP and have found that DAP does not induce autophagy, apoptosis or cell viability but does reduce cell proliferation. Our results suggest that an extraribosomal function of RPS19 involves the regulation of vascular endothelial growth factor (VEGF) but not EGF, PDGF or FGF. Engagement of RPS19 by DAP was shown by CETSA and ITDRF_CETSA assays, and knocking down of RPS19 with siRNA increased the potency of DAP in MCF7 cells. In addition, DAP suppressed the secretion of VEGF in cancer cells and thereby inhibited cell migration. Collectively, these data provide an outline of the underlying mechanism of how DAP exhibits anti-cancer activity and suggests that RPS19 could be a promising target for the development of new anticancer drugs.

Original language	English
Pages (from-to)	726-733
Number of pages	8
Journal	Journal of Antibiotics
Volume	74
Issue number	10
DOIs	https://doi.org/10.1038/s41429-021-00446-x
Publication status	Published - 2021 Oct

Bibliographical note

Funding Information:
Acknowledgements This work was partly supported by grants from the National Research Foundation of Korea (MSIP; 2015K1A1A2028365, 2015M3A9C4076321), the Brain Korea 21Four Project in the Republic of Korea, and ICONS (Institute of Convergence Science), Yonsei University and the ARC discovery grant DP1301032.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to the Japan Antibiotics Research Association.

All Science Journal Classification (ASJC) codes

Pharmacology
Drug Discovery

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10.1038/s41429-021-00446-x

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title = "Daptomycin suppresses tumor migration and angiogenesis via binding to ribosomal protein S19 in humans",

abstract = "We have previously reported that daptomycin (DAP), a last resort antibiotic, binds to ribosomal protein S19 (RPS19) in humans and exhibits selective anti-cancer activity against MCF7 breast cancer cells. Here, we investigated the role of RPS19 in the anti-cancer effects of DAP and have found that DAP does not induce autophagy, apoptosis or cell viability but does reduce cell proliferation. Our results suggest that an extraribosomal function of RPS19 involves the regulation of vascular endothelial growth factor (VEGF) but not EGF, PDGF or FGF. Engagement of RPS19 by DAP was shown by CETSA and ITDRFCETSA assays, and knocking down of RPS19 with siRNA increased the potency of DAP in MCF7 cells. In addition, DAP suppressed the secretion of VEGF in cancer cells and thereby inhibited cell migration. Collectively, these data provide an outline of the underlying mechanism of how DAP exhibits anti-cancer activity and suggests that RPS19 could be a promising target for the development of new anticancer drugs.",

author = "Cho, {Sung Min} and Lee, {Hwa Jung} and Peter Karuso and Kwon, {Ho Jeong}",

note = "Funding Information: Acknowledgements This work was partly supported by grants from the National Research Foundation of Korea (MSIP; 2015K1A1A2028365, 2015M3A9C4076321), the Brain Korea 21Four Project in the Republic of Korea, and ICONS (Institute of Convergence Science), Yonsei University and the ARC discovery grant DP1301032. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to the Japan Antibiotics Research Association.",

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N2 - We have previously reported that daptomycin (DAP), a last resort antibiotic, binds to ribosomal protein S19 (RPS19) in humans and exhibits selective anti-cancer activity against MCF7 breast cancer cells. Here, we investigated the role of RPS19 in the anti-cancer effects of DAP and have found that DAP does not induce autophagy, apoptosis or cell viability but does reduce cell proliferation. Our results suggest that an extraribosomal function of RPS19 involves the regulation of vascular endothelial growth factor (VEGF) but not EGF, PDGF or FGF. Engagement of RPS19 by DAP was shown by CETSA and ITDRFCETSA assays, and knocking down of RPS19 with siRNA increased the potency of DAP in MCF7 cells. In addition, DAP suppressed the secretion of VEGF in cancer cells and thereby inhibited cell migration. Collectively, these data provide an outline of the underlying mechanism of how DAP exhibits anti-cancer activity and suggests that RPS19 could be a promising target for the development of new anticancer drugs.

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Daptomycin suppresses tumor migration and angiogenesis via binding to ribosomal protein S19 in humans

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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