PMID- 23213464
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20121206
LR  - 20211021
IS  - 2046-6390 (Print)
IS  - 2046-6390 (Electronic)
IS  - 2046-6390 (Linking)
VI  - 1
IP  - 8
DP  - 2012 Aug 15
TI  - Adhesion rings surround invadopodia and promote maturation.
PG  - 711-22
LID - 10.1242/bio.20121867 [doi]
AB  - Invasion and metastasis are aggressive cancer phenotypes that are highly related 
      to the ability of cancer cells to degrade extracellular matrix (ECM). At the 
      cellular level, specialized actin-rich structures called invadopodia mediate 
      focal matrix degradation by serving as exocytic sites for ECM-degrading 
      proteinases. Adhesion signaling is likely to be a critical regulatory input to 
      invadopodia, but the mechanism and location of such adhesion signaling events are 
      poorly understood. Here, we report that adhesion rings surround invadopodia 
      shortly after formation and correlate strongly with invadopodium activity on a 
      cell-by-cell basis. By contrast, there was little correlation of focal adhesion 
      number or size with cellular invadopodium activity. Prevention of adhesion ring 
      formation by inhibition of RGD-binding integrins or knockdown (KD) of 
      integrin-linked kinase (ILK) reduced the number of ECM-degrading invadopodia and 
      reduced recruitment of IQGAP to invadopodium actin puncta. Furthermore, live cell 
      imaging revealed that the rate of extracellular MT1-MMP accumulation at 
      invadopodia was greatly reduced in both integrin-inhibited and ILK-KD cells. 
      Conversely, KD of MT1-MMP reduced invadopodium activity and dynamics but not the 
      number of adhesion-ringed invadopodia. These results suggest a model in which 
      adhesion rings are recruited to invadopodia shortly after formation and promote 
      invadopodium maturation by enhancing proteinase secretion. Since adhesion rings 
      are a defining characteristic of podosomes, similar structures formed by normal 
      cells, our data also suggest further similarities between invadopodia and 
      podosomes.
FAU - Branch, Kevin M
AU  - Branch KM
AD  - Department of Cancer Biology, Vanderbilt University School of Medicine , 
      Nashville, TN 37232 , USA.
FAU - Hoshino, Daisuke
AU  - Hoshino D
FAU - Weaver, Alissa M
AU  - Weaver AM
LA  - eng
GR  - P60 DK020593/DK/NIDDK NIH HHS/United States
GR  - P30 DK058404/DK/NIDDK NIH HHS/United States
GR  - P30 HD015052/HD/NICHD NIH HHS/United States
GR  - P30 EY008126/EY/NEI NIH HHS/United States
GR  - P30 DK020593/DK/NIDDK NIH HHS/United States
GR  - P30 CA068485/CA/NCI NIH HHS/United States
GR  - R01 GM075126/GM/NIGMS NIH HHS/United States
GR  - U01 CA143069/CA/NCI NIH HHS/United States
GR  - U24 DK059637/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20120612
PL  - England
TA  - Biol Open
JT  - Biology open
JID - 101578018
PMC - PMC3507228
OTO - NOTNLM
OT  - Adhesion rings
OT  - ILK
OT  - Integrin
OT  - Invadopodia
OT  - Invasion
OT  - MT1-MMP
COIS- Competing interests: The authors declare that there are no competing interests.
EDAT- 2012/12/06 06:00
MHDA- 2012/12/06 06:01
PMCR- 2012/06/12
CRDT- 2012/12/06 06:00
PHST- 2012/05/03 00:00 [received]
PHST- 2012/05/21 00:00 [accepted]
PHST- 2012/12/06 06:00 [entrez]
PHST- 2012/12/06 06:00 [pubmed]
PHST- 2012/12/06 06:01 [medline]
PHST- 2012/06/12 00:00 [pmc-release]
AID - BIO20121867 [pii]
AID - 10.1242/bio.20121867 [doi]
PST - ppublish
SO  - Biol Open. 2012 Aug 15;1(8):711-22. doi: 10.1242/bio.20121867. Epub 2012 Jun 12.