Targeting RPL39 and MLF2 reduces tumor initiation and metastasis in breast cancer by inhibiting nitric oxide synthase signaling

Research output: Contribution to journalArticle

Bhuvanesh Dave, Sergio Granados-Principal, Rui Zhu, Stephen Benz, Shahrooz Rabizadeh, Patrick Soon-Shiong, Ke Da Yu, Zhimin Shao, Xiaoxian Li, Michael Gilcrease, Zhao Lai, Yidong Chen, Tim H M Huang, Haifa Shen, Xuewu Liu, Mauro Ferrari, Ming Zhan, Stephen T. Wong, Muthiah Kumaraswami, Vivek Mittal & 3 others Xi Chen, Steven S. Gross, Jenny C. Chang

We previously described a gene signature for breast cancer stem cells (BCSCs) derived from patient biopsies. Selective shRNA knockdown identified ribosomal protein L39 (RPL39) and myeloid leukemia factor 2 (MLF2) as the top candidates that affect BCSC self-renewal. Knock-down of RPL39 and MLF2 by specific siRNA nanoparticles in patient-derived and human cancer xenografts reduced tumor volume and lung metastases with a concomitant decrease in BCSCs. RNA deep sequencing identified damaging mutations in both genes. These mutations were confirmed in patient lung metastases (n = 53) and were statistically associated with shorter median time to pulmonary metastasis. Both genes affect the nitric oxide synthase pathway and are altered by hypoxia. These findings support that extensive tumor heterogeneity exists within primary cancers; distinct subpopulations associated with stem-like properties have increased metastatic potential.

Original languageEnglish
Pages (from-to)8838-8843
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number24
DOIs
StatePublished - Jan 1 2014

PMID: 24876273

PMCID: PMC4066479

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Targeting RPL39 and MLF2 reduces tumor initiation and metastasis in breast cancer by inhibiting nitric oxide synthase signaling. / Dave, Bhuvanesh; Granados-Principal, Sergio; Zhu, Rui; Benz, Stephen; Rabizadeh, Shahrooz; Soon-Shiong, Patrick; Yu, Ke Da; Shao, Zhimin; Li, Xiaoxian; Gilcrease, Michael; Lai, Zhao; Chen, Yidong; Huang, Tim H M; Shen, Haifa; Liu, Xuewu; Ferrari, Mauro; Zhan, Ming; Wong, Stephen T.; Kumaraswami, Muthiah; Mittal, Vivek; Chen, Xi; Gross, Steven S.; Chang, Jenny C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 24, 01.01.2014, p. 8838-8843.

Research output: Contribution to journalArticle

Harvard

Dave, B, Granados-Principal, S, Zhu, R, Benz, S, Rabizadeh, S, Soon-Shiong, P, Yu, KD, Shao, Z, Li, X, Gilcrease, M, Lai, Z, Chen, Y, Huang, THM, Shen, H, Liu, X, Ferrari, M, Zhan, M, Wong, ST, Kumaraswami, M, Mittal, V, Chen, X, Gross, SS & Chang, JC 2014, 'Targeting RPL39 and MLF2 reduces tumor initiation and metastasis in breast cancer by inhibiting nitric oxide synthase signaling' Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 24, pp. 8838-8843. https://doi.org/10.1073/pnas.1320769111

APA

Dave, B., Granados-Principal, S., Zhu, R., Benz, S., Rabizadeh, S., Soon-Shiong, P., ... Chang, J. C. (2014). Targeting RPL39 and MLF2 reduces tumor initiation and metastasis in breast cancer by inhibiting nitric oxide synthase signaling. Proceedings of the National Academy of Sciences of the United States of America, 111(24), 8838-8843. https://doi.org/10.1073/pnas.1320769111

Vancouver

Dave B, Granados-Principal S, Zhu R, Benz S, Rabizadeh S, Soon-Shiong P et al. Targeting RPL39 and MLF2 reduces tumor initiation and metastasis in breast cancer by inhibiting nitric oxide synthase signaling. Proceedings of the National Academy of Sciences of the United States of America. 2014 Jan 1;111(24):8838-8843. https://doi.org/10.1073/pnas.1320769111

Author

Dave, Bhuvanesh ; Granados-Principal, Sergio ; Zhu, Rui ; Benz, Stephen ; Rabizadeh, Shahrooz ; Soon-Shiong, Patrick ; Yu, Ke Da ; Shao, Zhimin ; Li, Xiaoxian ; Gilcrease, Michael ; Lai, Zhao ; Chen, Yidong ; Huang, Tim H M ; Shen, Haifa ; Liu, Xuewu ; Ferrari, Mauro ; Zhan, Ming ; Wong, Stephen T. ; Kumaraswami, Muthiah ; Mittal, Vivek ; Chen, Xi ; Gross, Steven S. ; Chang, Jenny C. / Targeting RPL39 and MLF2 reduces tumor initiation and metastasis in breast cancer by inhibiting nitric oxide synthase signaling. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 24. pp. 8838-8843.

BibTeX

@article{c6b2119c2fb14f429bf1f7376976500f,
title = "Targeting RPL39 and MLF2 reduces tumor initiation and metastasis in breast cancer by inhibiting nitric oxide synthase signaling",
abstract = "We previously described a gene signature for breast cancer stem cells (BCSCs) derived from patient biopsies. Selective shRNA knockdown identified ribosomal protein L39 (RPL39) and myeloid leukemia factor 2 (MLF2) as the top candidates that affect BCSC self-renewal. Knock-down of RPL39 and MLF2 by specific siRNA nanoparticles in patient-derived and human cancer xenografts reduced tumor volume and lung metastases with a concomitant decrease in BCSCs. RNA deep sequencing identified damaging mutations in both genes. These mutations were confirmed in patient lung metastases (n = 53) and were statistically associated with shorter median time to pulmonary metastasis. Both genes affect the nitric oxide synthase pathway and are altered by hypoxia. These findings support that extensive tumor heterogeneity exists within primary cancers; distinct subpopulations associated with stem-like properties have increased metastatic potential.",
author = "Bhuvanesh Dave and Sergio Granados-Principal and Rui Zhu and Stephen Benz and Shahrooz Rabizadeh and Patrick Soon-Shiong and Yu, {Ke Da} and Zhimin Shao and Xiaoxian Li and Michael Gilcrease and Zhao Lai and Yidong Chen and Huang, {Tim H M} and Haifa Shen and Xuewu Liu and Mauro Ferrari and Ming Zhan and Wong, {Stephen T.} and Muthiah Kumaraswami and Vivek Mittal and Xi Chen and Gross, {Steven S.} and Chang, {Jenny C.}",
year = "2014",
month = "1",
day = "1",
doi = "10.1073/pnas.1320769111",
language = "English",
volume = "111",
pages = "8838--8843",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
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RIS

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T1 - Targeting RPL39 and MLF2 reduces tumor initiation and metastasis in breast cancer by inhibiting nitric oxide synthase signaling

AU - Dave, Bhuvanesh

AU - Granados-Principal, Sergio

AU - Zhu, Rui

AU - Benz, Stephen

AU - Rabizadeh, Shahrooz

AU - Soon-Shiong, Patrick

AU - Yu, Ke Da

AU - Shao, Zhimin

AU - Li, Xiaoxian

AU - Gilcrease, Michael

AU - Lai, Zhao

AU - Chen, Yidong

AU - Huang, Tim H M

AU - Shen, Haifa

AU - Liu, Xuewu

AU - Ferrari, Mauro

AU - Zhan, Ming

AU - Wong, Stephen T.

AU - Kumaraswami, Muthiah

AU - Mittal, Vivek

AU - Chen, Xi

AU - Gross, Steven S.

AU - Chang, Jenny C.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - We previously described a gene signature for breast cancer stem cells (BCSCs) derived from patient biopsies. Selective shRNA knockdown identified ribosomal protein L39 (RPL39) and myeloid leukemia factor 2 (MLF2) as the top candidates that affect BCSC self-renewal. Knock-down of RPL39 and MLF2 by specific siRNA nanoparticles in patient-derived and human cancer xenografts reduced tumor volume and lung metastases with a concomitant decrease in BCSCs. RNA deep sequencing identified damaging mutations in both genes. These mutations were confirmed in patient lung metastases (n = 53) and were statistically associated with shorter median time to pulmonary metastasis. Both genes affect the nitric oxide synthase pathway and are altered by hypoxia. These findings support that extensive tumor heterogeneity exists within primary cancers; distinct subpopulations associated with stem-like properties have increased metastatic potential.

AB - We previously described a gene signature for breast cancer stem cells (BCSCs) derived from patient biopsies. Selective shRNA knockdown identified ribosomal protein L39 (RPL39) and myeloid leukemia factor 2 (MLF2) as the top candidates that affect BCSC self-renewal. Knock-down of RPL39 and MLF2 by specific siRNA nanoparticles in patient-derived and human cancer xenografts reduced tumor volume and lung metastases with a concomitant decrease in BCSCs. RNA deep sequencing identified damaging mutations in both genes. These mutations were confirmed in patient lung metastases (n = 53) and were statistically associated with shorter median time to pulmonary metastasis. Both genes affect the nitric oxide synthase pathway and are altered by hypoxia. These findings support that extensive tumor heterogeneity exists within primary cancers; distinct subpopulations associated with stem-like properties have increased metastatic potential.

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U2 - 10.1073/pnas.1320769111

DO - 10.1073/pnas.1320769111

M3 - Article

VL - 111

SP - 8838

EP - 8843

JO - Proceedings of the National Academy of Sciences of the United States of America

T2 - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 24

ER -

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