Rab25 and CLIC3 Collaborate to Promote Integrin Recycling from Late Endosomes/Lysosomes and Drive Cancer Progression

Marta A. Dozynkiewicz; Nigel B. Jamieson; Iain MacPherson; Joan Grindlay; Peter V E vandenBerghe; Anne vonThun; Jennifer P. Morton; Charlie Gourley; Paul Timpson; Colin Nixon; Colin J. McKay; Ross Carter; David Strachan; Kurt Anderson; Owen J. Sansom; Patrick T. Caswell; Jim C. Norman

doi:10.1016/j.devcel.2011.11.008

Rab25 and CLIC3 Collaborate to Promote Integrin Recycling from Late Endosomes/Lysosomes and Drive Cancer Progression

Marta A. Dozynkiewicz, Nigel B. Jamieson, Iain MacPherson, Joan Grindlay, Peter V E vandenBerghe, Anne vonThun, Jennifer P. Morton, Charlie Gourley, Paul Timpson, Colin Nixon, Colin J. McKay, Ross Carter, David Strachan, Kurt Anderson, Owen J. Sansom, Patrick T. Caswell, Jim C. Norman

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

Abstract

Here we show that Rab25 permits the sorting of ligand-occupied, active-conformation α5β1 integrin to late endosomes/lysosomes. Photoactivation and biochemical approaches show that lysosomally targeted integrins are not degraded but are retrogradely transported and recycled to the plasma membrane at the back of invading cells. This requires CLIC3, a protein upregulated in Rab25-expressing cells and tumors, which colocalizes with active α5β1 in late endosomes/lysosomes. CLIC3 is necessary for release of the cell rear during migration on 3D matrices and is required for invasion and maintenance of active Src signaling in organotypic microenvironments. CLIC3 expression predicts lymph node metastasis and poor prognosis in operable cases of pancreatic ductal adenocarcinoma (PDAC). The identification of CLIC3 as a regulator of a recycling pathway and as an independent prognostic indicator in PDAC highlights the importance of active integrin trafficking as a potential drive to cancer progression invivo. © 2012 Elsevier Inc.

Original language	English
Pages (from-to)	131-145
Number of pages	14
Journal	Developmental cell
Volume	22
Issue number	1
DOIs	https://doi.org/10.1016/j.devcel.2011.11.008
Publication status	Published - 17 Jan 2012

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Dozynkiewicz, M. A., Jamieson, N. B., MacPherson, I., Grindlay, J., vandenBerghe, P. V. E., vonThun, A., Morton, J. P., Gourley, C., Timpson, P., Nixon, C., McKay, C. J., Carter, R., Strachan, D., Anderson, K., Sansom, O. J., Caswell, P. T., & Norman, J. C. (2012). Rab25 and CLIC3 Collaborate to Promote Integrin Recycling from Late Endosomes/Lysosomes and Drive Cancer Progression. Developmental cell, 22(1), 131-145. https://doi.org/10.1016/j.devcel.2011.11.008

@article{101765d0a1c04e648efb1d5a9f4862a6,

title = "Rab25 and CLIC3 Collaborate to Promote Integrin Recycling from Late Endosomes/Lysosomes and Drive Cancer Progression",

abstract = "Here we show that Rab25 permits the sorting of ligand-occupied, active-conformation α5β1 integrin to late endosomes/lysosomes. Photoactivation and biochemical approaches show that lysosomally targeted integrins are not degraded but are retrogradely transported and recycled to the plasma membrane at the back of invading cells. This requires CLIC3, a protein upregulated in Rab25-expressing cells and tumors, which colocalizes with active α5β1 in late endosomes/lysosomes. CLIC3 is necessary for release of the cell rear during migration on 3D matrices and is required for invasion and maintenance of active Src signaling in organotypic microenvironments. CLIC3 expression predicts lymph node metastasis and poor prognosis in operable cases of pancreatic ductal adenocarcinoma (PDAC). The identification of CLIC3 as a regulator of a recycling pathway and as an independent prognostic indicator in PDAC highlights the importance of active integrin trafficking as a potential drive to cancer progression invivo. {\textcopyright} 2012 Elsevier Inc.",

author = "Dozynkiewicz, {Marta A.} and Jamieson, {Nigel B.} and Iain MacPherson and Joan Grindlay and vandenBerghe, {Peter V E} and Anne vonThun and Morton, {Jennifer P.} and Charlie Gourley and Paul Timpson and Colin Nixon and McKay, {Colin J.} and Ross Carter and David Strachan and Kurt Anderson and Sansom, {Owen J.} and Caswell, {Patrick T.} and Norman, {Jim C.}",

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doi = "10.1016/j.devcel.2011.11.008",

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Dozynkiewicz, MA, Jamieson, NB, MacPherson, I, Grindlay, J, vandenBerghe, PVE, vonThun, A, Morton, JP, Gourley, C, Timpson, P, Nixon, C, McKay, CJ, Carter, R, Strachan, D, Anderson, K, Sansom, OJ, Caswell, PT & Norman, JC 2012, 'Rab25 and CLIC3 Collaborate to Promote Integrin Recycling from Late Endosomes/Lysosomes and Drive Cancer Progression', Developmental cell, vol. 22, no. 1, pp. 131-145. https://doi.org/10.1016/j.devcel.2011.11.008

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T1 - Rab25 and CLIC3 Collaborate to Promote Integrin Recycling from Late Endosomes/Lysosomes and Drive Cancer Progression

AU - Dozynkiewicz, Marta A.

AU - Jamieson, Nigel B.

AU - MacPherson, Iain

AU - Grindlay, Joan

AU - vandenBerghe, Peter V E

AU - vonThun, Anne

AU - Morton, Jennifer P.

AU - Gourley, Charlie

AU - Timpson, Paul

AU - Nixon, Colin

AU - McKay, Colin J.

AU - Carter, Ross

AU - Strachan, David

AU - Anderson, Kurt

AU - Sansom, Owen J.

AU - Caswell, Patrick T.

AU - Norman, Jim C.

PY - 2012/1/17

Y1 - 2012/1/17

N2 - Here we show that Rab25 permits the sorting of ligand-occupied, active-conformation α5β1 integrin to late endosomes/lysosomes. Photoactivation and biochemical approaches show that lysosomally targeted integrins are not degraded but are retrogradely transported and recycled to the plasma membrane at the back of invading cells. This requires CLIC3, a protein upregulated in Rab25-expressing cells and tumors, which colocalizes with active α5β1 in late endosomes/lysosomes. CLIC3 is necessary for release of the cell rear during migration on 3D matrices and is required for invasion and maintenance of active Src signaling in organotypic microenvironments. CLIC3 expression predicts lymph node metastasis and poor prognosis in operable cases of pancreatic ductal adenocarcinoma (PDAC). The identification of CLIC3 as a regulator of a recycling pathway and as an independent prognostic indicator in PDAC highlights the importance of active integrin trafficking as a potential drive to cancer progression invivo. © 2012 Elsevier Inc.

AB - Here we show that Rab25 permits the sorting of ligand-occupied, active-conformation α5β1 integrin to late endosomes/lysosomes. Photoactivation and biochemical approaches show that lysosomally targeted integrins are not degraded but are retrogradely transported and recycled to the plasma membrane at the back of invading cells. This requires CLIC3, a protein upregulated in Rab25-expressing cells and tumors, which colocalizes with active α5β1 in late endosomes/lysosomes. CLIC3 is necessary for release of the cell rear during migration on 3D matrices and is required for invasion and maintenance of active Src signaling in organotypic microenvironments. CLIC3 expression predicts lymph node metastasis and poor prognosis in operable cases of pancreatic ductal adenocarcinoma (PDAC). The identification of CLIC3 as a regulator of a recycling pathway and as an independent prognostic indicator in PDAC highlights the importance of active integrin trafficking as a potential drive to cancer progression invivo. © 2012 Elsevier Inc.

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DO - 10.1016/j.devcel.2011.11.008

M3 - Article

C2 - 22197222

SN - 1878-1551

VL - 22

SP - 131

EP - 145

JO - Developmental cell

JF - Developmental cell

IS - 1

ER -

Rab25 and CLIC3 Collaborate to Promote Integrin Recycling from Late Endosomes/Lysosomes and Drive Cancer Progression

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