PMID- 21720706
OWN - NLM
STAT- MEDLINE
DCOM- 20120113
LR  - 20110801
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 39
IP  - 4
DP  - 2011 Oct
TI  - Syntaxins 3 and 4 mediate vesicular trafficking of alpha5beta1 and alpha3beta1 integrins and 
      cancer cell migration.
PG  - 863-71
LID - 10.3892/ijo.2011.1101 [doi]
AB  - Integrins, a family of heterodimeric receptors for cell adhesion to the 
      extracellular matrix (ECM), play key roles in cell migration, cancer progression 
      and metastasis. As transmembrane proteins, integrins are transported in vesicles 
      and delivered to the cell surface by vesicular trafficking. The final step for 
      integrin delivery, i.e., fusion of integrin-containing vesicles with the plasma 
      membrane, is poorly understood at the molecular level. The SNARE (soluble 
      N-ethylmaleimide-sensitive factor attachment protein receptor) proteins syntaxins 
      1, 2, 3 and 4 are present at the plasma membrane to drive vesicle fusion. In this 
      study, we examined the roles of syntaxins 1, 2, 3 and 4 in vesicular trafficking 
      of alpha5beta1 and alpha3beta1 integrins. We showed that syntaxins 2, 3 and 4 were expressed in 
      HeLa cervical adenocarcinoma cells and PANC-1 pancreatic adenocarcinoma cells. In 
      migrating HeLa and PANC-1 cells, syntaxins 2, 3 and 4 co-localized with the lipid 
      raft constituent GM1 ganglioside at the leading edge. siRNA knockdown (KD) of 
      syntaxins 3 and 4, but not of syntaxin 2, in HeLa cells reduced cell surface 
      expression of alpha5beta1 and alpha3beta1 integrins and accumulated the integrins in 
      cytoplasmic vesicles, indicating that syntaxins 3 and 4 mediate vesicular 
      trafficking of alpha5beta1 and alpha3beta1 integrins to the cell surface. In addition, KD of 
      syntaxins 3 and 4 inhibited cell adhesion to fibronectin, suppressed chemotactic 
      cell migration and triggered apoptosis. Collectively, these data suggest that 
      syntaxins 3- and 4-dependent integrin trafficking is important in cancer cell 
      migration and survival, and may be a valuable target for cancer therapy.
FAU - Day, Paul
AU  - Day P
AD  - Department of Biochemistry and Molecular Biology, University of Louisville School 
      of Medicine, Louisville, KY 40202, USA.
FAU - Riggs, Krista A
AU  - Riggs KA
FAU - Hasan, Nazarul
AU  - Hasan N
FAU - Corbin, Deborah
AU  - Corbin D
FAU - Humphrey, David
AU  - Humphrey D
FAU - Hu, Chuan
AU  - Hu C
LA  - eng
GR  - CA135123/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110628
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Fibronectins)
RN  - 0 (Integrin alpha3beta1)
RN  - 0 (Integrin alpha5beta1)
RN  - 0 (Qa-SNARE Proteins)
RN  - 0 (SNARE Proteins)
SB  - IM
MH  - Apoptosis/physiology
MH  - Cell Adhesion/physiology
MH  - Cell Line, Tumor
MH  - Cell Membrane/metabolism
MH  - Cell Movement/*physiology
MH  - Fibronectins/metabolism
MH  - Gene Knockdown Techniques/methods
MH  - HeLa Cells
MH  - Humans
MH  - Integrin alpha3beta1/antagonists & inhibitors/*metabolism
MH  - Integrin alpha5beta1/antagonists & inhibitors/*metabolism
MH  - Membrane Microdomains/metabolism
MH  - Neoplasms/genetics/metabolism/*pathology
MH  - Protein Transport
MH  - Pseudopodia/metabolism
MH  - Qa-SNARE Proteins/genetics/*metabolism
MH  - SNARE Proteins/metabolism
MH  - Transport Vesicles/*metabolism
EDAT- 2011/07/02 06:00
MHDA- 2012/01/14 06:00
CRDT- 2011/07/02 06:00
PHST- 2011/03/17 00:00 [received]
PHST- 2011/05/10 00:00 [accepted]
PHST- 2011/07/02 06:00 [entrez]
PHST- 2011/07/02 06:00 [pubmed]
PHST- 2012/01/14 06:00 [medline]
AID - 10.3892/ijo.2011.1101 [doi]
PST - ppublish
SO  - Int J Oncol. 2011 Oct;39(4):863-71. doi: 10.3892/ijo.2011.1101. Epub 2011 Jun 28.