The functional roles of cytoskeleton protein adducin 3 in glioblastoma multiforme

Abstract

Objective:

Adducin is a membrane skeleton protein encoded by distinct genes mapped to different chromosomes, referred to as ADD1, ADD2 and ADD3. Adducin primarily functions in the assembly of spectrin-actin network that provides physical support to the plasma membrane, also mediates signal transduction in various cell physiological processes upon regulation by PKC-dependent and calcium/calmodulin dependent pathways. Dysregulation of adducin may contribute to alterations in cellular functions involved in pathological pathways. These aberrations are associated with wide range of diseases and may confer risks in cancer. In this study, we aim to characterize the role of ADD3 in glioblastoma and determine how it may contribute in glioma pathogenesis.

Method:

Bioinformatics analyses were performed to determine the expression profile of ADD3 in glioblastoma as compared to its normal counterparts. We have characterized the functional roles of ADD3 by in vitro loss of function studies. The molecular alterations were identified by immunofluorescence staining, western blot and qPCR analyses.

Result:

We found that ADD3 expression is differentially expressed in between GBM with ADD3 high and low patients. Bioinformatics analysis suggested that low ADD3 expressions maybe involved in activating DNA damage checkpoints. Our findings also validate that loss of ADD3 would induced mitotic defects, reduced glioma cell proliferation, cell migration and increased apoptosis.

Conclusion:

This study is ongoing, and it’s the first study that reports the functional role of ADD3 in GBM beyond those as a structural protein. Results implicated that ADD3 may serve as a novel target in glioblastoma and deserves further investigation.