Alpha-actinin 1 and alpha-actinin 4: contrasting roles in the survival, motility, and RhoA signaling of astrocytoma cells.
Alpha-actinin is a prominent actin filament associated protein for which different isoforms exist. Here, we have examined whether the two highly homologous non-muscle alpha-actinin isoforms 1 and 4 exhibit functional differences in astrocytoma cells. The protein levels of these isoforms were differentially regulated during the development and progression of astrocytomas, as alpha-actinin 1 was higher in astrocytomas compared to normal brains whereas alpha-actinin 4 was elevated in high-grade astrocytomas compared to normal brains and low grade astrocytomas. RNAi demonstrated contrasted contributions of alpha-actinin 1 and 4 to the malignant behavior of U-373, U-87 and A172 astrocytoma cells. While alpha-actinin 1 appeared to favor the expansion of U-373, U-87 and A172 astrocytoma cell populations, alpha-actinin 4 played this role only for U-373 cells. On the other hand, downregulation of alpha-actinin 4, but not 1, reduced cell motility, adhesion, cortical actin, and RhoA levels. Finally, in the three astrocytoma cell lines examined, alpha-actinin 1 and 4 had contrasted biochemical properties as alpha-actinin 4 was significantly more abundant in the actin cytoskeleton than alpha-actinin 1. Collectively, these findings suggest that alpha-actinin 1 and 4 are differentially regulated during the development and progression of astrocytomas because each of these isoforms uniquely contributes to distinct malignant properties of astrocytoma cells.
Department of Biology, Grambling State University, Grambling, LA 71245, USA.
Quincy
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Quick
Omar
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Skalli
D000185:Actinin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D020742:rhoA GTP-Binding Protein / Q000378:metabolism / Q000502:physiology*
C526905:ACTN1 protein, human; C111453:ACTN4 protein, human; D000185:Actinin; D020742:rhoA GTP-Binding Protein