P-Rex1 is required for efficient melanoblast migration and melanoma metastasis

被引：139

作者：

Lindsay, Colin R. ^{[1
]}

Lawn, Samuel ^{[1
]}

Campbell, Andrew D. ^{[1
]}

Faller, William J. ^{[1
]}

Rambow, Florian ^{[2
]}

Mort, Richard L. ^{[3
]}

Timpson, Paul ^{[1
]}

Li, Ang ^{[1
]}

Cammareri, Patrizia ^{[1
]}

Ridgway, Rachel A. ^{[1
]}

Morton, Jennifer P. ^{[1
]}

Doyle, Brendan ^{[1
]}

Hegarty, Shauna ^{[4
]}

Rafferty, Mairin ^{[5
]}

Murphy, Ian G. ^{[6
]}

McDermott, Enda W. ^{[6
]}

Sheahan, Kieran ^{[6
]}

Pedone, Katherine ^{[7
]}

Finn, Alexander J. ^{[7
]}

Groben, Pamela A. ^{[7
]}

Thomas, Nancy E. ^{[7
]}

Hao, Honglin ^{[7
]}

Carson, Craig ^{[7
]}

Norman, Jim C. ^{[1
]}

Machesky, Laura M. ^{[1
]}

Gallagher, William M. ^{[5
]}

Jackson, Ian J. ^{[3
]}

Van Kempen, Leon ^{[8
]}

Beermann, Friedrich ^{[9
]}

Der, Channing ^{[7
]}

Larue, Lionel ^{[2
]}

Welch, Heidi C. ^{[10
]}

Ozanne, Brad W. ^{[1
]}

Sansom, Owen J. ^{[1
]}

机构：

[1] Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland

[2] Inst Curie, INSERM, Ctr Rech, U1021, F-91405 Paris, France

[3] MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland

[4] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Belfast BT7 1NN, Antrim, North Ireland

[5] Univ Coll, UCD Conway Inst, UCD Sch Biomol & Biomed Sci, Dublin 4, Ireland

[6] St Vincents Univ Hosp, Dept Surg, Dublin 4, Ireland

[7] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27514 USA

[8] McGill Univ, Jewish Gen Hosp, Dept Pathol, Montreal, PQ H3A 2B4, Canada

[9] ISREC SV EPFL, CH-1066 Epalinges, Switzerland

[10] Babraham Inst, Cambridge CB22 3AT, England

来源：

NATURE COMMUNICATIONS | 2011年 / 2卷

基金：

英国医学研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

RAS SUPERFAMILY; CANCER; RAC1; PROLIFERATION; XENOGRAFTS; ACTIVATION; EXPRESSION; INVASION; TIAM1; BRAF;

D O I：

10.1038/ncomms1560

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：

Metastases are the major cause of death from melanoma, a skin cancer that has the fastest rising incidence of any malignancy in the Western world. Molecular pathways that drive melanoblast migration in development are believed to underpin the movement and ultimately the metastasis of melanoma. Here we show that mice lacking P-Rex1, a Rac-specific Rho GTPase guanine nucleotide exchange factor, have a melanoblast migration defect during development evidenced by a white belly. Moreover, these P-Rex1(-/-) mice are resistant to metastasis when crossed to a murine model of melanoma. Mechanistically, this is associated with P-Rex1 driving invasion in a Rac-dependent manner. P-Rex1 is elevated in the majority of human melanoma cell lines and tumour tissue. We conclude that P-Rex1 has an important role in melanoblast migration and cancer progression to metastasis in mice and humans.

引用

页数：9

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