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

Colin R Lindsay; Samuel Lawn; Andrew D Campbell; William J Faller; Florian Rambow; Richard L Mort; Paul Timpson; Ang Li; Patrizia Cammareri; Rachel A Ridgway; Jennifer P Morton; Brendan Doyle; Shauna Hegarty; Mairin Rafferty; Ian G Murphy; Enda W McDermott; Kieran Sheahan; Katherine Pedone; Alexander J Finn; Pamela A Groben; Nancy E Thomas; Honglin Hao; Craig Carson; Jim C Norman; Laura M Machesky; William M Gallagher; Ian J Jackson; Leon Van Kempen; Friedrich Beermann; Channing Der; Lionel Larue; Heidi C Welch; Brad W Ozanne; Owen J Sansom

doi:10.1038/ncomms1560

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

Colin R Lindsay, Samuel Lawn, Andrew D Campbell, William J Faller, Florian Rambow, Richard L Mort, Paul Timpson, Ang Li, Patrizia Cammareri, Rachel A Ridgway, Jennifer P Morton, Brendan Doyle, Shauna Hegarty, Mairin Rafferty, Ian G Murphy, Enda W McDermott, Kieran Sheahan, Katherine Pedone, Alexander J Finn, Pamela A GrobenNancy E Thomas, Honglin Hao, Craig Carson, Jim C Norman, Laura M Machesky, William M Gallagher, Ian J Jackson, Leon Van Kempen, Friedrich Beermann, Channing Der, Lionel Larue, Heidi C Welch, Brad W Ozanne, Owen J Sansom^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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.

Original language	English
Article number	555
Number of pages	9
Journal	Nature Communications
Volume	2
DOIs	https://doi.org/10.1038/ncomms1560
Publication status	Published - 22-Nov-2011

Keywords

Animals
Cell Movement/genetics
Cells, Cultured
Guanine Nucleotide Exchange Factors/genetics
Humans
Immunohistochemistry
In Vitro Techniques
Melanoma/genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Neoplasm Metastasis/genetics
Tissue Array Analysis

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P-Rex1 is required for efficient melanoblast migration and melanoma metastasisFinal publisher's version, 2.89 MBLicence: CC BY-NC-SA

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Lindsay, C. R., Lawn, S., Campbell, A. D., Faller, W. J., Rambow, F., Mort, R. L., Timpson, P., Li, A., Cammareri, P., Ridgway, R. A., Morton, J. P., Doyle, B., Hegarty, S., Rafferty, M., Murphy, I. G., McDermott, E. W., Sheahan, K., Pedone, K., Finn, A. J., ... Sansom, O. J. (2011). P-Rex1 is required for efficient melanoblast migration and melanoma metastasis. Nature Communications, 2, Article 555. https://doi.org/10.1038/ncomms1560

@article{ba14929f85584523a3585edad1e287be,

title = "P-Rex1 is required for efficient melanoblast migration and melanoma metastasis",

abstract = "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.",

keywords = "Animals, Cell Movement/genetics, Cells, Cultured, Guanine Nucleotide Exchange Factors/genetics, Humans, Immunohistochemistry, In Vitro Techniques, Melanoma/genetics, Mice, Mice, Inbred C57BL, Mice, Knockout, Neoplasm Metastasis/genetics, Tissue Array Analysis",

author = "Lindsay, {Colin R} and Samuel Lawn and Campbell, {Andrew D} and Faller, {William J} and Florian Rambow and Mort, {Richard L} and Paul Timpson and Ang Li and Patrizia Cammareri and Ridgway, {Rachel A} and Morton, {Jennifer P} and Brendan Doyle and Shauna Hegarty and Mairin Rafferty and Murphy, {Ian G} and McDermott, {Enda W} and Kieran Sheahan and Katherine Pedone and Finn, {Alexander J} and Groben, {Pamela A} and Thomas, {Nancy E} and Honglin Hao and Craig Carson and Norman, {Jim C} and Machesky, {Laura M} and Gallagher, {William M} and Jackson, {Ian J} and {Van Kempen}, Leon and Friedrich Beermann and Channing Der and Lionel Larue and Welch, {Heidi C} and Ozanne, {Brad W} and Sansom, {Owen J}",

year = "2011",

month = nov,

day = "22",

doi = "10.1038/ncomms1560",

language = "English",

volume = "2",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Lindsay, CR, Lawn, S, Campbell, AD, Faller, WJ, Rambow, F, Mort, RL, Timpson, P, Li, A, Cammareri, P, Ridgway, RA, Morton, JP, Doyle, B, Hegarty, S, Rafferty, M, Murphy, IG, McDermott, EW, Sheahan, K, Pedone, K, Finn, AJ, Groben, PA, Thomas, NE, Hao, H, Carson, C, Norman, JC, Machesky, LM, Gallagher, WM, Jackson, IJ, Van Kempen, L, Beermann, F, Der, C, Larue, L, Welch, HC, Ozanne, BW & Sansom, OJ 2011, 'P-Rex1 is required for efficient melanoblast migration and melanoma metastasis', Nature Communications, vol. 2, 555. https://doi.org/10.1038/ncomms1560

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/genetics

KW - Cells, Cultured

KW - Guanine Nucleotide Exchange Factors/genetics

KW - Humans

KW - Immunohistochemistry

KW - In Vitro Techniques

KW - Melanoma/genetics

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Neoplasm Metastasis/genetics

KW - Tissue Array Analysis

U2 - 10.1038/ncomms1560

DO - 10.1038/ncomms1560

M3 - Article

C2 - 22109529

SN - 2041-1723

VL - 2

JO - Nature Communications

JF - Nature Communications

M1 - 555

ER -

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

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Keywords

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