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 & 13 others Theodoros G. Soldatos, David B. Jackson, John E. Wiktorowicz, Madeline Torres-Lugo, Tom Young, Koenraad De Geest, Gary E. Gallick, Menashe Bar-Eli, Gabriel Lopez-Berestein, Steve W. Cole, Gustavo E. Lopez, Susan K. Lutgendorf, Anil K. Sood

Research output: Contribution to journalArticle

106 Citations (Scopus)

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 languageEnglish (US)
Article number1403
JournalNature Communications
Volume4
DOIs
StatePublished - 2013
Externally publishedYes

Fingerprint

metastasis
Tumors
tumors
switches
cancer
Chemical activation
Switches
activation
Neoplasm Metastasis
Adrenergic Agents
adrenergics
Norepinephrine
Cells
Neoplasms
Phosphorylation
disrupting
phosphorylation
Tumor Microenvironment
mortality
regulators

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Armaiz-Pena, G. N., Allen, J. K., Cruz, A., Stone, R. L., Nick, A. M., Lin, Y. G., ... Sood, A. K. (2013). Src activation by adrenoreceptors is a key switch for tumour metastasis. Nature Communications, 4, [1403]. https://doi.org/10.1038/ncomms2413

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

In: Nature Communications, Vol. 4, 1403, 2013.

Research output: Contribution to journalArticle

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
Armaiz-Pena GN, Allen JK, Cruz A, Stone RL, Nick AM, Lin YG et al. Src activation by adrenoreceptors is a key switch for tumour metastasis. Nature Communications. 2013;4. 1403. https://doi.org/10.1038/ncomms2413
Armaiz-Pena, Guillermo N. ; Allen, Julie K. ; Cruz, Anthony ; Stone, Rebecca L. ; Nick, Alpa M. ; Lin, Yvonne G. ; Han, Liz Y. ; Mangala, Lingegowda S. ; Villares, Gabriel J. ; Vivas-Mejia, Pablo ; Rodriguez-Aguayo, Cristian ; Nagaraja, Archana S. ; Gharpure, Kshipra M. ; Wu, Zheng ; English, Robert D. ; Soman, Kizhake V. ; Shahzad, Mian M K ; Zigler, Maya ; Deavers, Michael T. ; Zien, Alexander ; Soldatos, Theodoros G. ; Jackson, David B. ; Wiktorowicz, John E. ; Torres-Lugo, Madeline ; Young, Tom ; De Geest, Koenraad ; Gallick, Gary E. ; Bar-Eli, Menashe ; Lopez-Berestein, Gabriel ; Cole, Steve W. ; Lopez, Gustavo E. ; Lutgendorf, Susan K. ; Sood, Anil K. / Src activation by adrenoreceptors is a key switch for tumour metastasis. In: Nature Communications. 2013 ; Vol. 4.
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AU - Deavers, Michael T.

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AU - Soldatos, Theodoros G.

AU - Jackson, David B.

AU - Wiktorowicz, John E.

AU - Torres-Lugo, Madeline

AU - Young, Tom

AU - De Geest, Koenraad

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AU - Bar-Eli, Menashe

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