Rab25 Associates with α5β1 Integrin to Promote Invasive Migration in 3D Microenvironments

Patrick T. Caswell; Heather J. Spence; Maddy Parsons; Dominic P. White; Katherine Clark; Kwai Wa Cheng; Gordon B. Mills; Martin J. Humphries; Anthea J. Messent; Kurt I. Anderson; Mary W. McCaffrey; Bradford W. Ozanne; Jim C. Norman

doi:10.1016/j.devcel.2007.08.012

Rab25 Associates with α5β1 Integrin to Promote Invasive Migration in 3D Microenvironments

Patrick T. Caswell, Heather J. Spence, Maddy Parsons, Dominic P. White, Katherine Clark, Kwai Wa Cheng, Gordon B. Mills, Martin J. Humphries, Anthea J. Messent, Kurt I. Anderson, Mary W. McCaffrey, Bradford W. Ozanne, Jim C. Norman

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

339 Scopus citations

Abstract

Here, we report a direct interaction between the β1 integrin cytoplasmic tail and Rab25, a GTPase that has been linked to tumor aggressiveness and metastasis. Rab25 promotes a mode of migration on 3D matrices that is characterized by the extension of long pseudopodia, and the association of the GTPase with α5β1 promotes localization of vesicles that deliver integrin to the plasma membrane at pseudopodial tips as well as the retention of a pool of cycling α5β1 at the cell front. Furthermore, Rab25-driven tumor-cell invasion into a 3D extracellular matrix environment is strongly dependent on ligation of fibronectin by α5β1 integrin and the capacity of Rab25 to interact with β1 integrin. These data indicate that Rab25 contributes to tumor progression by directing the localization of integrin-recycling vesicles and thereby enhancing the ability of tumor cells to invade the extracellular matrix.

Original language	English (US)
Pages (from-to)	496-510
Number of pages	15
Journal	Developmental Cell
Volume	13
Issue number	4
DOIs	https://doi.org/10.1016/j.devcel.2007.08.012
State	Published - Oct 9 2007
Externally published	Yes

Keywords

CELLBIO

ASJC Scopus subject areas

Molecular Biology
General Biochemistry, Genetics and Molecular Biology
Developmental Biology
Cell Biology

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10.1016/j.devcel.2007.08.012

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Caswell, P. T., Spence, H. J., Parsons, M., White, D. P., Clark, K., Cheng, K. W., Mills, G. B., Humphries, M. J., Messent, A. J., Anderson, K. I., McCaffrey, M. W., Ozanne, B. W., & Norman, J. C. (2007). Rab25 Associates with α5β1 Integrin to Promote Invasive Migration in 3D Microenvironments. Developmental Cell, 13(4), 496-510. https://doi.org/10.1016/j.devcel.2007.08.012

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title = "Rab25 Associates with α5β1 Integrin to Promote Invasive Migration in 3D Microenvironments",

abstract = "Here, we report a direct interaction between the β1 integrin cytoplasmic tail and Rab25, a GTPase that has been linked to tumor aggressiveness and metastasis. Rab25 promotes a mode of migration on 3D matrices that is characterized by the extension of long pseudopodia, and the association of the GTPase with α5β1 promotes localization of vesicles that deliver integrin to the plasma membrane at pseudopodial tips as well as the retention of a pool of cycling α5β1 at the cell front. Furthermore, Rab25-driven tumor-cell invasion into a 3D extracellular matrix environment is strongly dependent on ligation of fibronectin by α5β1 integrin and the capacity of Rab25 to interact with β1 integrin. These data indicate that Rab25 contributes to tumor progression by directing the localization of integrin-recycling vesicles and thereby enhancing the ability of tumor cells to invade the extracellular matrix.",

keywords = "CELLBIO",

author = "Caswell, {Patrick T.} and Spence, {Heather J.} and Maddy Parsons and White, {Dominic P.} and Katherine Clark and Cheng, {Kwai Wa} and Mills, {Gordon B.} and Humphries, {Martin J.} and Messent, {Anthea J.} and Anderson, {Kurt I.} and McCaffrey, {Mary W.} and Ozanne, {Bradford W.} and Norman, {Jim C.}",

year = "2007",

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doi = "10.1016/j.devcel.2007.08.012",

language = "English (US)",

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pages = "496--510",

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T1 - Rab25 Associates with α5β1 Integrin to Promote Invasive Migration in 3D Microenvironments

AU - Caswell, Patrick T.

AU - Spence, Heather J.

AU - Parsons, Maddy

AU - White, Dominic P.

AU - Clark, Katherine

AU - Cheng, Kwai Wa

AU - Mills, Gordon B.

AU - Humphries, Martin J.

AU - Messent, Anthea J.

AU - Anderson, Kurt I.

AU - McCaffrey, Mary W.

AU - Ozanne, Bradford W.

AU - Norman, Jim C.

PY - 2007/10/9

Y1 - 2007/10/9

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AB - Here, we report a direct interaction between the β1 integrin cytoplasmic tail and Rab25, a GTPase that has been linked to tumor aggressiveness and metastasis. Rab25 promotes a mode of migration on 3D matrices that is characterized by the extension of long pseudopodia, and the association of the GTPase with α5β1 promotes localization of vesicles that deliver integrin to the plasma membrane at pseudopodial tips as well as the retention of a pool of cycling α5β1 at the cell front. Furthermore, Rab25-driven tumor-cell invasion into a 3D extracellular matrix environment is strongly dependent on ligation of fibronectin by α5β1 integrin and the capacity of Rab25 to interact with β1 integrin. These data indicate that Rab25 contributes to tumor progression by directing the localization of integrin-recycling vesicles and thereby enhancing the ability of tumor cells to invade the extracellular matrix.

KW - CELLBIO

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ER -

Rab25 Associates with α5β1 Integrin to Promote Invasive Migration in 3D Microenvironments

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