PMID- 23740575 OWN - NLM STAT- MEDLINE DCOM- 20131230 LR - 20211021 IS - 2046-2441 (Electronic) IS - 2046-2441 (Linking) VI - 3 IP - 6 DP - 2013 Jun 5 TI - Hypoxia-induced invadopodia formation: a role for beta-PIX. PG - 120159 LID - 10.1098/rsob.120159 [doi] LID - 120159 AB - During tumour progression, oxygen tension in the microenvironment surrounding tumour cells is reduced, resulting in hypoxia. It is well 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 recently HIF-1alpha 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-1alpha has not been explored. We now report that HIF-1alpha is a driver of invadopodia formation. Furthermore, we have identified an important, direct and novel link between the Rho family activator beta-PIX, HIF-1alpha and invadopodia formation. Indeed, we find that beta-PIX expression is essential for invadopodia formation. In conclusion, we identify a new HIF-1alpha mechanistic pathway and suggest that beta-PIX is a novel downstream signalling mediator during invadopodia formation. FAU - Md Hashim, Nur Fariesha AU - Md Hashim NF AD - Division of Cancer Studies, King's College London, London SE1 1UL, UK. FAU - Nicholas, Nicole S AU - Nicholas NS FAU - Dart, Anna E AU - Dart AE FAU - Kiriakidis, Serafim AU - Kiriakidis S FAU - Paleolog, Ewa AU - Paleolog E FAU - Wells, Claire M AU - Wells CM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130605 PL - England TA - Open Biol JT - Open biology JID - 101580419 RN - 0 (ARHGEF7 protein, human) RN - 0 (Amino Acids, Dicarboxylic) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - 0 (Rho Guanine Nucleotide Exchange Factors) RN - VVW38EB8YS (oxalylglycine) SB - IM MH - Amino Acids, Dicarboxylic/pharmacology MH - *Cell Hypoxia MH - Cell Line, Tumor MH - HEK293 Cells MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism MH - RNA Interference MH - RNA, Messenger/metabolism MH - RNA, Small Interfering/metabolism MH - Rho Guanine Nucleotide Exchange Factors/antagonists & inhibitors/genetics/*metabolism MH - Up-Regulation/drug effects PMC - PMC3718326 OTO - NOTNLM OT - hypoxia OT - invadopodia OT - beta-PIX EDAT- 2013/06/07 06:00 MHDA- 2014/01/01 06:00 PMCR- 2013/06/01 CRDT- 2013/06/07 06:00 PHST- 2013/06/07 06:00 [entrez] PHST- 2013/06/07 06:00 [pubmed] PHST- 2014/01/01 06:00 [medline] PHST- 2013/06/01 00:00 [pmc-release] AID - rsob.120159 [pii] AID - rsob120159 [pii] AID - 10.1098/rsob.120159 [doi] PST - epublish SO - Open Biol. 2013 Jun 5;3(6):120159. doi: 10.1098/rsob.120159.