Degradation of cofilin is regulated by Cbl, AIP4 and Syk resulting in increased migration of LMP2A positive nasopharyngeal carcinoma cells

Abstract Expression of cofilin is directly associated with metastatic activity in many tumors. Here, we studied the role of Latent Membrane Protein 2 A (LMP2A) of Epstein-Barr Virus (EBV) in the accumulation of cofilin observed in nasopharyngeal cancer (NPC) tumor cells. We used LMP2A transformed NP...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Murat R. Gainullin, Ilya Yu Zhukov, Xiaoying Zhou, Yingxi Mo, Lidiia Astakhova, Ingemar Ernberg, Liudmila Matskova
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2017
Materias:
R
Q
Acceso en línea:https://doaj.org/article/41a7fdc60fbc4b3b8fa6d0711f9d76f6
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
Descripción
Sumario:Abstract Expression of cofilin is directly associated with metastatic activity in many tumors. Here, we studied the role of Latent Membrane Protein 2 A (LMP2A) of Epstein-Barr Virus (EBV) in the accumulation of cofilin observed in nasopharyngeal cancer (NPC) tumor cells. We used LMP2A transformed NPC cell lines to analyze cofilin expression. We used mutation analysis, ectopic expression and down-regulation of Cbl, AIP4 and Syk in these cell lines to determine the effect of the LMP2A viral protein on cofilin degradation and its role in the assembly of a cofilin degrading protein complex. The LMP2A of EBV was found to interfer with cofilin degradation in NPC cells by accelerating the proteasomal degradation of Cbl and Syk. In line with this, we found significantly higher cofilin expression in NPC tumor samples as compared to the surrounding epithelial tissues. Cofilin, as an actin severing protein, influences cellular plasticity, and facilitates cellular movement in response to oncogenic stimuli. Thus, under relaxed cellular control, cofilin facilitates tumor cell movement and dissemination. Interference with its degradation may enhance the metastatic potential of NPC cells.