EPAC2: A new and promising protein for glioma pathogenesis and therapy

Abstract

Gliomas are prime brain cancers which are initiated by malignant modification of neural stem cells, progenitor cells and differentiated glial cells such as astrocyte, oligodendrocyte as well as ependymal cells. Exchange proteins directly activated by cAMP (EPACs) are crucial cyclic adenosine 3’,5’-monophosphate (cAMP)-determined signaling pathways. Cyclic AMP-intermediated signaling events were utilized to transduce protein kinase A (PKA) leading to the detection of EPACs or cAMP-guanine exchange factors (cAMP-GEFs). EPACs have been detected as crucial proteins associated with the pathogenesis of neurological disorders as well as numerous human diseases. EPAC proteins have two isoforms. These isoforms are EPAC1 and EPAC2. EPAC2 also known as Rap guanine nucleotide exchange factor 4 (RAPGEF4) is generally expression in all neurites. Higher EAPC2 levels was detected in the cortex, hippocampus as well as striatum of adult mouse brain. Activation as well as over-secretion of EPAC2 triggers apoptosis in neurons and EPAC-triggered apoptosis was intermediated via the modulation of Bcl-2 interacting member protein (BIM). EPAC2 secretory levels has proven to be more in low-grade clinical glioma than high-grade clinical glioma. This review therefore explores the effects of EPAC2/RAPGEF4 on the pathogenesis of glioma instead of EPAC1 because EPAC2 and not EPAC1 is predominately expressed in the brain. Therefore, EPAC2 is most likely to modulate glioma pathogenesis rather than EPAC1.

The Pivotal Immunomodulatory and Anti-Inflammatory Effect of Histone-Lysine N-Methyltransferase in the Glioma Microenvironment: Its Biomarker and Therapy Potentials

“…These lesions are histologically grouped into Grades I-IV according to the World Health Organization (WHO) criteria [ 4 , 5 ]. Most frequently, Grade I gliomas are detected in children and they mostly have good outcomes [ 1 , 4 ]. However, Grade II gliomas are often associated with hypercellularity and have a 5-8-year average survival rate [ 4 , 6 ].…”

“…Most frequently, Grade I gliomas are detected in children and they mostly have good outcomes [ 1 , 4 ]. However, Grade II gliomas are often associated with hypercellularity and have a 5-8-year average survival rate [ 4 , 6 ]. Furthermore, Grade III comprises astrocytoma or anaplastic astrocytoma based on histological classification [ 4 ].…”

“…However, Grade II gliomas are often associated with hypercellularity and have a 5-8-year average survival rate [ 4 , 6 ]. Furthermore, Grade III comprises astrocytoma or anaplastic astrocytoma based on histological classification [ 4 ]. They are depicted with hypercellularity, nuclear atypia, and mitotic characters [ 4 ].…”

“…Furthermore, Grade III comprises astrocytoma or anaplastic astrocytoma based on histological classification [ 4 ]. They are depicted with hypercellularity, nuclear atypia, and mitotic characters [ 4 ]. The anaplastic astrocytoma has a 3-year average survival rate [ 1 , 7 , 8 ].…”

“…The anaplastic astrocytoma has a 3-year average survival rate [ 1 , 7 , 8 ]. Glioblastoma multiforme (GBM) comprises Grade IV gliomas [ 1 , 4 ].…”