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

被引：172

作者：

Armaiz-Pena, Guillermo N. ^{[1
]}

Allen, Julie K. ^{[1
,2
]}

Cruz, Anthony ^{[3
]}

Stone, Rebecca L. ^{[1
]}

Nick, Alpa M. ^{[1
]}

Lin, Yvonne G. ^{[1
]}

Han, Liz Y. ^{[1
]}

Mangala, Lingegowda S. ^{[1
,4
]}

Villares, Gabriel J. ^{[2
,5
]}

Vivas-Mejia, Pablo ^{[6
,7
,8
]}

Rodriguez-Aguayo, Cristian ^{[6
]}

Nagaraja, Archana S. ^{[1
,2
]}

Gharpure, Kshipra M. ^{[1
,2
]}

Wu, Zheng ^{[9
,10
]}

English, Robert D. ^{[9
]}

Soman, Kizhake V. ^{[9
,10
]}

Shazhad, Mian M. K. ^{[1
]}

Zigler, Maya ^{[2
,5
]}

Deavers, Michael T. ^{[11
]}

Zien, Alexander ^{[12
]}

Soldatos, Theodoros G. ^{[12
]}

Jackson, David B. ^{[12
]}

Wiktorowicz, John E. ^{[9
,10
]}

Torres-Lugo, Madeline ^{[13
]}

Young, Tom ^{[14
]}

De Geest, Koen ^{[15
]}

Gallick, Gary E. ^{[16
]}

Bar-Eli, Menashe ^{[5
]}

Lopez-Berestein, Gabriel ^{[4
,5
,6
]}

Cole, Steve W. ^{[17
]}

Lopez, Gustavo E. ^{[3
]}

Lutgendorf, Susan K. ^{[15
,18
,19
]}

Sood, Anil K. ^{[1
,4
,5
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA

[2] Univ Texas Hlth Sci Ctr, Canc Biol Program, Grad Sch Biomed Sci, Houston, TX 77030 USA

[3] Univ Puerto Rico, Dept Chem, Mayaguez, PR 00681 USA

[4] Univ Texas MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNA, Houston, TX 77030 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA

[7] Univ Puerto Rico, Dept Biochem, San Juan, PR 00935 USA

[8] Univ Puerto Rico, Ctr Canc, San Juan, PR 00935 USA

[9] Univ Texas Med Branch, Biomol Resource Facil, Galveston, TX 77555 USA

[10] Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA

[11] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

[12] Mol Hlth GmbH, D-69115 Heidelberg, Germany

[13] Univ Puerto Rico, Dept Chem Engn, Mayaguez, PR 00681 USA

[14] CUNY Herbert H Lehman Coll, Dept Chem, Bronx, NY 10468 USA

[15] Univ Iowa, Div Gynecol Oncol, Dept Obstet & Gynecol, Iowa City, IA 52242 USA

[16] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA

[17] Univ Calif Los Angeles, Div Hematol Oncol, Dept Med, Los Angeles, CA 90095 USA

[18] Univ Iowa, Dept Psychol & Urol, Iowa City, IA 52242 USA

[19] Univ Iowa, Holden Comprehens Canc Ctr, Iowa City, IA 52242 USA

来源：

NATURE COMMUNICATIONS | 2013年 / 4卷

关键词：

PATHWAY INVOLVING SRC; PKA PHOSPHORYLATION; BROWN ADIPOCYTES; TYROSINE KINASE; GENE-EXPRESSION; GROWTH; NOREPINEPHRINE; PROTEIN; FAMILY; DEPRESSION;

D O I：

10.1038/ncomms2413

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

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