PMID- 20037648
OWN - NLM
STAT- MEDLINE
DCOM- 20100317
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 4
IP  - 12
DP  - 2009 Dec 23
TI  - Isoform-specific contributions of alpha-actinin to glioma cell mechanobiology.
PG  - e8427
LID - 10.1371/journal.pone.0008427 [doi]
LID - e8427
AB  - Glioblastoma Multiforme (GBM) is a malignant astrocytic tumor associated with low 
      survival rates because of aggressive infiltration of tumor cells into the brain 
      parenchyma. Expression of the actin binding protein alpha-actinin has been 
      strongly correlated with the invasive phenotype of GBM in vivo. To probe the 
      cellular basis of this correlation, we have suppressed expression of the 
      nonmuscle isoforms alpha-actinin-1 and alpha-actinin-4 and examined the 
      contribution of each isoform to the structure, mechanics, and motility of human 
      glioma tumor cells in culture. While subcellular localization of each isoform is 
      distinct, suppression of either isoform yields a phenotype that includes 
      dramatically reduced motility, compensatory upregulation and redistribution of 
      vinculin, reduced cortical elasticity, and reduced ability to adapt to changes in 
      the elasticity of the extracellular matrix (ECM). Mechanistic studies reveal a 
      relationship between alpha-actinin and non-muscle myosin II in which depletion of 
      either alpha-actinin isoform reduces myosin expression and maximal cell-ECM 
      tractional forces. Our results demonstrate that both alpha-actinin-1 and 
      alpha-actinin-4 make critical and distinct contributions to cytoskeletal 
      organization, rigidity-sensing, and motility of glioma cells, thereby yielding 
      mechanistic insight into the observed correlation between alpha-actinin 
      expression and GBM invasiveness in vivo.
FAU - Sen, Shamik
AU  - Sen S
AD  - Department of Bioengineering, University of California, Berkeley, California, 
      USA.
FAU - Dong, Meimei
AU  - Dong M
FAU - Kumar, Sanjay
AU  - Kumar S
LA  - eng
GR  - DP2 OD004213/OD/NIH HHS/United States
GR  - 1DP2OD004213/OD/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20091223
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Protein Isoforms)
RN  - 11003-00-2 (Actinin)
RN  - 125361-02-6 (Vinculin)
RN  - EC 3.6.4.1 (Myosins)
SB  - IM
MH  - Actinin/*metabolism
MH  - Animals
MH  - Biomechanical Phenomena
MH  - Cattle
MH  - Cell Movement
MH  - Extracellular Matrix/metabolism
MH  - Focal Adhesions/metabolism
MH  - Glioma/*metabolism/*pathology
MH  - Humans
MH  - Myosins/metabolism
MH  - Protein Binding
MH  - Protein Isoforms/metabolism
MH  - Protein Transport
MH  - Tumor Cells, Cultured
MH  - Vinculin/metabolism
PMC - PMC2793025
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2009/12/29 06:00
MHDA- 2010/03/18 06:00
PMCR- 2009/12/23
CRDT- 2009/12/29 06:00
PHST- 2009/07/22 00:00 [received]
PHST- 2009/12/01 00:00 [accepted]
PHST- 2009/12/29 06:00 [entrez]
PHST- 2009/12/29 06:00 [pubmed]
PHST- 2010/03/18 06:00 [medline]
PHST- 2009/12/23 00:00 [pmc-release]
AID - 09-PONE-RA-11822R1 [pii]
AID - 10.1371/journal.pone.0008427 [doi]
PST - epublish
SO  - PLoS One. 2009 Dec 23;4(12):e8427. doi: 10.1371/journal.pone.0008427.