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HS1-associated protein X-1 regulates carcinoma cell migration and invasion via clathrin-mediated endocytosis of integrin ?v?6

HS1-associated protein X-1 regulates carcinoma cell migration and invasion via clathrin-mediated endocytosis of integrin ?v?6
HS1-associated protein X-1 regulates carcinoma cell migration and invasion via clathrin-mediated endocytosis of integrin ?v?6
Enhanced expression levels of integrin ?v?6 have been linked to more aggressive invasive carcinoma cell behavior and poorer clinical prognosis. However, how alphavbeta6 determines invasion and the dynamics of integrin ?v?6 regulation in tumor cells are poorly understood. We have identified the 35-kDa HS1- associated protein X-1 (HAX-1) protein as a novel binding partner of the ?6 cytoplasmic tail using a yeast two-hybrid screen. We show that alphavbeta6 -dependent migration is blocked following small interfering RNA (siRNA)–mediated depletion of HAX-1 in oral squamous cell carcinoma cell lines. Using both siRNA and membrane-permeable peptides, we show that ?v?6-dependent migration and invasion require HAX-1 to bind directly to ?6 and thereby regulate clathrin-mediated endocytosis of ?v?6 integrins. Progression of oral cancer is associated with enhanced expression of alphavbeta6 and HAX-1 proteins in patient tissue. This report establishes that integrin endocytosis is required for ?v?6-dependent carcinoma cell motility and invasion and suggests that this process is an important mechanism in cancer progression.
0008-5472
5275-5284
Ramsay, Alan G.
f91140da-31d7-4904-aad6-a7640c70210e
Keppler, Melanie D.
6452c8eb-268a-47f4-955d-e1819df05333
Jazeyeri, Mona
f82597a4-c91b-424b-a6f5-d628cb81f3ac
Thomas, Gareth J.
2ff54aa9-a766-416b-91ee-cf1c5be74106
Parsons, Maddy
f1f69eab-ae49-403b-a50a-532d46edb7d4
Violette, Shelia
8ea6f92d-036a-4e84-ad05-7be701d84f4b
Weinreb, Paul
8656c784-208a-4814-83be-da3ff5878431
Hart, Ian R.
6a3728fc-5385-4dd4-a5e3-edd5168a0e8d
Marshall, John F.
1134b21f-7f23-4ee6-aaf5-c7580b73c10b
Ramsay, Alan G.
f91140da-31d7-4904-aad6-a7640c70210e
Keppler, Melanie D.
6452c8eb-268a-47f4-955d-e1819df05333
Jazeyeri, Mona
f82597a4-c91b-424b-a6f5-d628cb81f3ac
Thomas, Gareth J.
2ff54aa9-a766-416b-91ee-cf1c5be74106
Parsons, Maddy
f1f69eab-ae49-403b-a50a-532d46edb7d4
Violette, Shelia
8ea6f92d-036a-4e84-ad05-7be701d84f4b
Weinreb, Paul
8656c784-208a-4814-83be-da3ff5878431
Hart, Ian R.
6a3728fc-5385-4dd4-a5e3-edd5168a0e8d
Marshall, John F.
1134b21f-7f23-4ee6-aaf5-c7580b73c10b

Ramsay, Alan G., Keppler, Melanie D., Jazeyeri, Mona, Thomas, Gareth J., Parsons, Maddy, Violette, Shelia, Weinreb, Paul, Hart, Ian R. and Marshall, John F. (2007) HS1-associated protein X-1 regulates carcinoma cell migration and invasion via clathrin-mediated endocytosis of integrin ?v?6. Cancer Research, 67 (11), 5275-5284. (doi:10.1158/0008-5472.CAN-07-0318).

Record type: Article

Abstract

Enhanced expression levels of integrin ?v?6 have been linked to more aggressive invasive carcinoma cell behavior and poorer clinical prognosis. However, how alphavbeta6 determines invasion and the dynamics of integrin ?v?6 regulation in tumor cells are poorly understood. We have identified the 35-kDa HS1- associated protein X-1 (HAX-1) protein as a novel binding partner of the ?6 cytoplasmic tail using a yeast two-hybrid screen. We show that alphavbeta6 -dependent migration is blocked following small interfering RNA (siRNA)–mediated depletion of HAX-1 in oral squamous cell carcinoma cell lines. Using both siRNA and membrane-permeable peptides, we show that ?v?6-dependent migration and invasion require HAX-1 to bind directly to ?6 and thereby regulate clathrin-mediated endocytosis of ?v?6 integrins. Progression of oral cancer is associated with enhanced expression of alphavbeta6 and HAX-1 proteins in patient tissue. This report establishes that integrin endocytosis is required for ?v?6-dependent carcinoma cell motility and invasion and suggests that this process is an important mechanism in cancer progression.

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Published date: 1 June 2007

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Local EPrints ID: 66686
URI: http://eprints.soton.ac.uk/id/eprint/66686
ISSN: 0008-5472
PURE UUID: ec8e902c-dd5d-434c-8b23-b8f8d5a88c3e

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Date deposited: 14 Jul 2009
Last modified: 13 Mar 2024 18:30

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Contributors

Author: Alan G. Ramsay
Author: Melanie D. Keppler
Author: Mona Jazeyeri
Author: Maddy Parsons
Author: Shelia Violette
Author: Paul Weinreb
Author: Ian R. Hart
Author: John F. Marshall

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