Src activation by adrenoreceptors is a key switch for tumour metastasis

Guillermo N. Armaiz-Pena; Julie K. Allen; Anthony Cruz; Rebecca L. Stone; Alpa M. Nick; Yvonne G. Lin; Liz Y. Han; Lingegowda S. Mangala; Gabriel J. Villares; Pablo Vivas-Mejia; Cristian Rodriguez-Aguayo; Archana S. Nagaraja; Kshipra M. Gharpure; Zheng Wu; Robert D. English; Kizhake V. Soman; Mian M.K. Shahzad; Maya Zigler; Michael T. Deavers; Alexander Zien; Theodoros G. Soldatos; David B. Jackson; John E. Wiktorowicz; Madeline Torres-Lugo; Tom Young; Koen De Geest; Gary E. Gallick; Menashe Bar-Eli; Gabriel Lopez-Berestein; Steve W. Cole; Gustavo E. Lopez; Susan K. Lutgendorf; Anil K. Sood

doi:10.1038/ncomms2413

Src activation by adrenoreceptors is a key switch for tumour metastasis

Guillermo N. Armaiz-Pena, Julie K. Allen, Anthony Cruz, Rebecca L. Stone, Alpa M. Nick, Yvonne G. Lin, Liz Y. Han, Lingegowda S. Mangala, Gabriel J. Villares, Pablo Vivas-Mejia, Cristian Rodriguez-Aguayo, Archana S. Nagaraja, Kshipra M. Gharpure, Zheng Wu, Robert D. English, Kizhake V. Soman, Mian M.K. Shahzad, Maya Zigler, Michael T. Deavers, Alexander ZienTheodoros G. Soldatos, David B. Jackson, John E. Wiktorowicz, Madeline Torres-Lugo, Tom Young, Koen De Geest, Gary E. Gallick, Menashe Bar-Eli, Gabriel Lopez-Berestein, Steve W. Cole, Gustavo E. Lopez, Susan K. Lutgendorf, Anil K. Sood

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180 Scopus citations

Abstract

Noradrenaline can modulate multiple cellular functions important for cancer progression; however, how this single extracellular signal regulates such a broad array of cellular processes is unknown. Here we identify Src as a key regulator of phosphoproteomic signalling networks activated in response to beta-adrenergic signalling in cancer cells. These results also identify a new mechanism of Src phosphorylation that mediates beta-adrenergic/PKA regulation of downstream networks, thereby enhancing tumour cell migration, invasion and growth. In human ovarian cancer samples, high tumoural noradrenaline levels were correlated with high pSrc Y419 levels. Moreover, among cancer patients, the use of beta blockers was significantly associated with reduced cancer-related mortality. Collectively, these data provide a pivotal molecular target for disrupting neural signalling in the tumour microenvironment.

Original language	English (US)
Article number	1403
Journal	Nature communications
Volume	4
DOIs	https://doi.org/10.1038/ncomms2413
State	Published - 2013

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/ncomms2413

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Armaiz-Pena, G. N., Allen, J. K., Cruz, A., Stone, R. L., Nick, A. M., Lin, Y. G., Han, L. Y., Mangala, L. S., Villares, G. J., Vivas-Mejia, P., Rodriguez-Aguayo, C., Nagaraja, A. S., Gharpure, K. M., Wu, Z., English, R. D., Soman, K. V., Shahzad, M. M. K., Zigler, M., Deavers, M. T., ... Sood, A. K. (2013). Src activation by adrenoreceptors is a key switch for tumour metastasis. Nature communications, 4, Article 1403. https://doi.org/10.1038/ncomms2413

Armaiz-Pena, GN, Allen, JK, Cruz, A, Stone, RL, Nick, AM, Lin, YG, Han, LY, Mangala, LS, Villares, GJ, Vivas-Mejia, P, Rodriguez-Aguayo, C, Nagaraja, AS, Gharpure, KM, Wu, Z, English, RD, Soman, KV, Shahzad, MMK, Zigler, M, Deavers, MT, Zien, A, Soldatos, TG, Jackson, DB, Wiktorowicz, JE, Torres-Lugo, M, Young, T, De Geest, K, Gallick, GE, Bar-Eli, M, Lopez-Berestein, G, Cole, SW, Lopez, GE, Lutgendorf, SK & Sood, AK 2013, 'Src activation by adrenoreceptors is a key switch for tumour metastasis', Nature communications, vol. 4, 1403. https://doi.org/10.1038/ncomms2413

@article{53bc390d060942e4b08969c2ee7ab625,

title = "Src activation by adrenoreceptors is a key switch for tumour metastasis",

abstract = "Noradrenaline can modulate multiple cellular functions important for cancer progression; however, how this single extracellular signal regulates such a broad array of cellular processes is unknown. Here we identify Src as a key regulator of phosphoproteomic signalling networks activated in response to beta-adrenergic signalling in cancer cells. These results also identify a new mechanism of Src phosphorylation that mediates beta-adrenergic/PKA regulation of downstream networks, thereby enhancing tumour cell migration, invasion and growth. In human ovarian cancer samples, high tumoural noradrenaline levels were correlated with high pSrc Y419 levels. Moreover, among cancer patients, the use of beta blockers was significantly associated with reduced cancer-related mortality. Collectively, these data provide a pivotal molecular target for disrupting neural signalling in the tumour microenvironment.",

author = "Armaiz-Pena, {Guillermo N.} and Allen, {Julie K.} and Anthony Cruz and Stone, {Rebecca L.} and Nick, {Alpa M.} and Lin, {Yvonne G.} and Han, {Liz Y.} and Mangala, {Lingegowda S.} and Villares, {Gabriel J.} and Pablo Vivas-Mejia and Cristian Rodriguez-Aguayo and Nagaraja, {Archana S.} and Gharpure, {Kshipra M.} and Zheng Wu and English, {Robert D.} and Soman, {Kizhake V.} and Shahzad, {Mian M.K.} and Maya Zigler and Deavers, {Michael T.} and Alexander Zien and Soldatos, {Theodoros G.} and Jackson, {David B.} and Wiktorowicz, {John E.} and Madeline Torres-Lugo and Tom Young and {De Geest}, Koen and Gallick, {Gary E.} and Menashe Bar-Eli and Gabriel Lopez-Berestein and Cole, {Steve W.} and Lopez, {Gustavo E.} and Lutgendorf, {Susan K.} and Sood, {Anil K.}",

note = "Funding Information: GNA-P was supported, in part, by the NCI F31CA126474 Fellowship for Minority Students. Y.G.L., L.Y.H., A.M.N. and R.L.S. were supported by an NIH T32 Training Grant CA101642. S.K.L. was supported by NIH grants CA140933 and CA104825. M.M.S. was supported by the GCF-Molly Cade ovarian cancer research grant and the NIH/ NICHD Baylor WRHR scholarship grant. This work was also supported in part by NIH grants (CA110793 and CA109298, P50CA083639, P50CA098258, CA128797, RC2GM092599, U54CA151668, U54CA96300 and U54CA96297), the University of Texas Medical Branch NHLBI Proteomics Centre (contract HV-10-05_(2)), Ovarian Cancer Research Fund Programme Project Development Grant, Department of Defence (OC073399, W81XWH-10-1-0158, OC100237 and BC085265), the Zarrow Foundation, the Betty Ann Asche Murray Distinguished Professorship, the Marcus Foundation, the RGK Foundation, the Gilder Foundation, the estate of C.G. Johnson Jr, the Laura and John Arnold Foundation) and the Blanton-Davis Ovarian Cancer Research Programme. The authors thank Ms Donna Reynolds and Drs Robert Langley, and Philip Stork for helpful discussions, comments and for providing reagents. We would like to thank the High Performance Computing Facility of the University of Puerto Rico for the computer time.",

year = "2013",

doi = "10.1038/ncomms2413",

language = "English (US)",

volume = "4",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Src activation by adrenoreceptors is a key switch for tumour metastasis

AU - Armaiz-Pena, Guillermo N.

AU - Allen, Julie K.

AU - Cruz, Anthony

AU - Stone, Rebecca L.

AU - Nick, Alpa M.

AU - Lin, Yvonne G.

AU - Han, Liz Y.

AU - Mangala, Lingegowda S.

AU - Villares, Gabriel J.

AU - Vivas-Mejia, Pablo

AU - Rodriguez-Aguayo, Cristian

AU - Nagaraja, Archana S.

AU - Gharpure, Kshipra M.

AU - Wu, Zheng

AU - English, Robert D.

AU - Soman, Kizhake V.

AU - Shahzad, Mian M.K.

AU - Zigler, Maya

AU - Deavers, Michael T.

AU - Zien, Alexander

AU - Soldatos, Theodoros G.

AU - Jackson, David B.

AU - Wiktorowicz, John E.

AU - Torres-Lugo, Madeline

AU - Young, Tom

AU - De Geest, Koen

AU - Gallick, Gary E.

AU - Bar-Eli, Menashe

AU - Lopez-Berestein, Gabriel

AU - Cole, Steve W.

AU - Lopez, Gustavo E.

AU - Lutgendorf, Susan K.

AU - Sood, Anil K.

N1 - Funding Information: GNA-P was supported, in part, by the NCI F31CA126474 Fellowship for Minority Students. Y.G.L., L.Y.H., A.M.N. and R.L.S. were supported by an NIH T32 Training Grant CA101642. S.K.L. was supported by NIH grants CA140933 and CA104825. M.M.S. was supported by the GCF-Molly Cade ovarian cancer research grant and the NIH/ NICHD Baylor WRHR scholarship grant. This work was also supported in part by NIH grants (CA110793 and CA109298, P50CA083639, P50CA098258, CA128797, RC2GM092599, U54CA151668, U54CA96300 and U54CA96297), the University of Texas Medical Branch NHLBI Proteomics Centre (contract HV-10-05_(2)), Ovarian Cancer Research Fund Programme Project Development Grant, Department of Defence (OC073399, W81XWH-10-1-0158, OC100237 and BC085265), the Zarrow Foundation, the Betty Ann Asche Murray Distinguished Professorship, the Marcus Foundation, the RGK Foundation, the Gilder Foundation, the estate of C.G. Johnson Jr, the Laura and John Arnold Foundation) and the Blanton-Davis Ovarian Cancer Research Programme. The authors thank Ms Donna Reynolds and Drs Robert Langley, and Philip Stork for helpful discussions, comments and for providing reagents. We would like to thank the High Performance Computing Facility of the University of Puerto Rico for the computer time.

PY - 2013

Y1 - 2013

N2 - Noradrenaline can modulate multiple cellular functions important for cancer progression; however, how this single extracellular signal regulates such a broad array of cellular processes is unknown. Here we identify Src as a key regulator of phosphoproteomic signalling networks activated in response to beta-adrenergic signalling in cancer cells. These results also identify a new mechanism of Src phosphorylation that mediates beta-adrenergic/PKA regulation of downstream networks, thereby enhancing tumour cell migration, invasion and growth. In human ovarian cancer samples, high tumoural noradrenaline levels were correlated with high pSrc Y419 levels. Moreover, among cancer patients, the use of beta blockers was significantly associated with reduced cancer-related mortality. Collectively, these data provide a pivotal molecular target for disrupting neural signalling in the tumour microenvironment.

AB - Noradrenaline can modulate multiple cellular functions important for cancer progression; however, how this single extracellular signal regulates such a broad array of cellular processes is unknown. Here we identify Src as a key regulator of phosphoproteomic signalling networks activated in response to beta-adrenergic signalling in cancer cells. These results also identify a new mechanism of Src phosphorylation that mediates beta-adrenergic/PKA regulation of downstream networks, thereby enhancing tumour cell migration, invasion and growth. In human ovarian cancer samples, high tumoural noradrenaline levels were correlated with high pSrc Y419 levels. Moreover, among cancer patients, the use of beta blockers was significantly associated with reduced cancer-related mortality. Collectively, these data provide a pivotal molecular target for disrupting neural signalling in the tumour microenvironment.

UR - http://www.scopus.com/inward/record.url?scp=84877058177&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877058177&partnerID=8YFLogxK

U2 - 10.1038/ncomms2413

DO - 10.1038/ncomms2413

M3 - Article

C2 - 23360994

AN - SCOPUS:84877058177

SN - 2041-1723

VL - 4

JO - Nature communications

JF - Nature communications

M1 - 1403

ER -

Src activation by adrenoreceptors is a key switch for tumour metastasis

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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