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Intermediate filament protein synemin contributes to the migratory properties of astrocytoma cells by influencing the dynamics of the actin cytoskeleton

Yihang Pan^*,, Runfeng Jing^*,, Aaron Pitre^*,, Briana Jill Williams^, and Omar Skalli^*,,1

^* Department of Cellular Biology and Anatomy,

Department of Urology, and

Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA

¹Correspondence: Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, 1501 Kings Hwy., Shreveport, LA 71130, USA. E-mail: oskall{at}lsuhsc.edu

We have shown previously that, in astrocytoma cells, synemin is present at the leading edge, an unusual localization for an intermediate filament (IF) protein. Here, we report that synemin down-regulation with specific small hairpin RNAs (shRNAs) sharply decreased the migration of astrocytoma cells. The presence of synemin at the leading edge also correlated with a high migratory potential, as shown by comparing astrocytoma cells to carcinoma cells without synemin at the leading edge. Synemin-silenced astrocytoma cells were smaller and spread more slowly than controls. In addition, synemin silencing reduced proliferation without increasing apoptosis. The adhesion to substratum and distribution of vinculin in focal contacts of synemin-silenced astrocytoma cells were similar to those of controls. Synemin-silenced cells, however, exhibited a reduction in the amount of filamentous (F) -actin and of -actinin, but not of vinculin, associated with F-actin. Altogether, these results demonstrate that synemin is important for the malignant behavior of astrocytoma cells and that it contributes to the high motility of these cells by modulating the dynamics of -actinin and actin. —Pan, Y., Jing, R., Pitre, A., Williams, B. J., Skalli, O. Intermediate filament protein synemin contributes to the migratory properties of astrocytoma cells by influencing the dynamics of the actin cytoskeleton.

Key Words: glioma • invasion • -actinin