Research output: Contribution to Journal/Magazine › Journal article › peer-review
P-Rex1 is required for efficient melanoblast migration and melanoma metastasis. / Lindsay, Colin R.; Lawn, Samuel; Campbell, Andrew D. et al.
In: Nature Communications, Vol. 2, 555, 22.11.2011.Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - P-Rex1 is required for efficient melanoblast migration and melanoma metastasis
AU - Lindsay, Colin R.
AU - Lawn, Samuel
AU - Campbell, Andrew D.
AU - Faller, William J.
AU - Rambow, Florian
AU - Mort, Richard L.
AU - Timpson, Paul
AU - Li, Ang
AU - Cammareri, Patrizia
AU - Ridgway, Rachel A.
AU - Morton, Jennifer P.
AU - Doyle, Brendan
AU - Hegarty, Shauna
AU - Rafferty, Mairin
AU - Murphy, Ian G.
AU - McDermott, Enda W.
AU - Sheahan, Kieran
AU - Pedone, Katherine
AU - Finn, Alexander J.
AU - Groben, Pamela A.
AU - Thomas, Nancy E.
AU - Hao, Honglin
AU - Carson, Craig
AU - Norman, Jim C.
AU - Machesky, Laura M.
AU - Gallagher, William M.
AU - Jackson, Ian J.
AU - Van Kempen, Leon
AU - Beermann, Friedrich
AU - Der, Channing
AU - Larue, Lionel
AU - Welch, Heidi C.
AU - Ozanne, Brad W.
AU - Sansom, Owen J.
PY - 2011/11/22
Y1 - 2011/11/22
N2 - 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.
AB - 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.
KW - Animals
KW - Cell Movement
KW - Cells, Cultured
KW - Guanine Nucleotide Exchange Factors
KW - Humans
KW - Immunohistochemistry
KW - In Vitro Techniques
KW - Melanoma
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Neoplasm Metastasis
KW - Tissue Array Analysis
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, Non-U.S. Gov't
U2 - 10.1038/ncomms1560
DO - 10.1038/ncomms1560
M3 - Journal article
C2 - 22109529
VL - 2
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 555
ER -