Hypoxia-induced invadopodia formation : a role for β-PIX

During tumour progression, oxygen tension in the microenvironment surrounding tumour cells is reduced, resulting in hypoxia. It iswell established that cancer cells resist the negative effects of hypoxia by inducing angiogenesis predominantly via the activity of transcription factor hypoxia-inducibl...

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Main Authors: Md Hashim, Nur Fariesha, Nicholas, Nicole S., Dart, Anna E., Kiriakidis, Serafim, Paleolog, Ewa, Wells, Claire M.
Format: Article
Language:English
Published: The Royal Society 2013
Online Access:http://psasir.upm.edu.my/id/eprint/29799/1/Hypoxia.pdf
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author Md Hashim, Nur Fariesha
Nicholas, Nicole S.
Dart, Anna E.
Kiriakidis, Serafim
Paleolog, Ewa
Wells, Claire M.
author_facet Md Hashim, Nur Fariesha
Nicholas, Nicole S.
Dart, Anna E.
Kiriakidis, Serafim
Paleolog, Ewa
Wells, Claire M.
author_sort Md Hashim, Nur Fariesha
collection UPM
description During tumour progression, oxygen tension in the microenvironment surrounding tumour cells is reduced, resulting in hypoxia. It iswell established that cancer cells resist the negative effects of hypoxia by inducing angiogenesis predominantly via the activity of transcription factor hypoxia-inducible factor-1 (HIF-1). However, more recentlyHIF-1α has also been linked to increased invasive potential, although the molecular mechanisms remain to be defined. Invasive cancer cells are thought to employ membrane protrusions, termed invadopodia, to achieve matrix degradation. While many invadopodia components have been identified, signalling pathways that link extracellular stimuli to invadopodia formation remain largely unknown. Indeed, the relationship between invadopodia formation and HIF-1α has not been explored. We now report that HIF-1α is a driver of invadopodia formation. Furthermore, we have identified an important, direct and novel link between the Rho family activator β-PIX, HIF-1α and invadopodia formation. Indeed, we find that β-PIX expression is essential for invadopodia formation. In conclusion, we identify a new HIF-1α mechanistic pathway and suggest that β-PIX is a novel downstream signalling mediator during invadopodia formation.
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spelling upm.eprints-297992015-10-07T07:46:26Z http://psasir.upm.edu.my/id/eprint/29799/ Hypoxia-induced invadopodia formation : a role for β-PIX Md Hashim, Nur Fariesha Nicholas, Nicole S. Dart, Anna E. Kiriakidis, Serafim Paleolog, Ewa Wells, Claire M. During tumour progression, oxygen tension in the microenvironment surrounding tumour cells is reduced, resulting in hypoxia. It iswell established that cancer cells resist the negative effects of hypoxia by inducing angiogenesis predominantly via the activity of transcription factor hypoxia-inducible factor-1 (HIF-1). However, more recentlyHIF-1α has also been linked to increased invasive potential, although the molecular mechanisms remain to be defined. Invasive cancer cells are thought to employ membrane protrusions, termed invadopodia, to achieve matrix degradation. While many invadopodia components have been identified, signalling pathways that link extracellular stimuli to invadopodia formation remain largely unknown. Indeed, the relationship between invadopodia formation and HIF-1α has not been explored. We now report that HIF-1α is a driver of invadopodia formation. Furthermore, we have identified an important, direct and novel link between the Rho family activator β-PIX, HIF-1α and invadopodia formation. Indeed, we find that β-PIX expression is essential for invadopodia formation. In conclusion, we identify a new HIF-1α mechanistic pathway and suggest that β-PIX is a novel downstream signalling mediator during invadopodia formation. The Royal Society 2013-06-05 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/29799/1/Hypoxia.pdf Md Hashim, Nur Fariesha and Nicholas, Nicole S. and Dart, Anna E. and Kiriakidis, Serafim and Paleolog, Ewa and Wells, Claire M. (2013) Hypoxia-induced invadopodia formation : a role for β-PIX. Open Biology , 3 (June). art. no. 120159. pp. 1-10. ISSN 2046-2441; ESSN: 2046-2441 10.1098/rsob.120159
spellingShingle Md Hashim, Nur Fariesha
Nicholas, Nicole S.
Dart, Anna E.
Kiriakidis, Serafim
Paleolog, Ewa
Wells, Claire M.
Hypoxia-induced invadopodia formation : a role for β-PIX
title Hypoxia-induced invadopodia formation : a role for β-PIX
title_full Hypoxia-induced invadopodia formation : a role for β-PIX
title_fullStr Hypoxia-induced invadopodia formation : a role for β-PIX
title_full_unstemmed Hypoxia-induced invadopodia formation : a role for β-PIX
title_short Hypoxia-induced invadopodia formation : a role for β-PIX
title_sort hypoxia induced invadopodia formation a role for β pix
url http://psasir.upm.edu.my/id/eprint/29799/1/Hypoxia.pdf
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