Implications of mitogen-activated protein kinase signaling in glioma.
Gliomas are the most common primary central nervous system tumors. Gliomas originate from astrocytes, oligodendrocytes, and neural stem cells or their precursors. According to WHO classification, gliomas are classified into four different malignant grades ranging from grade I to grade IV based on histopathological features and related molecular aberrations. The induction and maintenance of these tumors can be attributed largely to aberrant signaling networks. In this regard, the mitogen-activated protein kinase (MAPK) network has been widely studied and is reported to be severely altered in glial tumors. Mutations in MAPK pathways most frequently affect RAS and B-RAF in the ERK, c-Jun N-terminal kinase (JNK), and p38 pathways leading to malignant transformation. Also, it is linked to both inherited and sequential accumulations of mutations that control receptor tyrosine kinase (RTK)-activated signal transduction pathways, cell cycle growth arrest pathways, and nonresponsive cell death pathways. Genetic alterations that modulate RTK signaling can also alter several downstream pathways, including RAS-mediated MAP kinases along with JNK pathways, which ultimately regulate cell proliferation and cell death. The present review focuses on recent literature regarding important deregulations in the RTK-activated MAPK pathway during gliomagenesis and progression.
Laboratory of Neuroscience, Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, AP, India.
Vimal
V
Pandey
Laboratory of Neuroscience, Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, AP, India.
Vasantha Kumar
VK
Bhaskara
Laboratory of Neuroscience, Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, AP, India.
Phanithi Prakash
PP
Babu
D001932:Brain Neoplasms / Q000201:enzymology*; D005910:Glioma / Q000201:enzymology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D020928:Mitogen-Activated Protein Kinases
EGF/EGFR; ERK; JNK; MAP kinases; glioma; p38 MAPK; receptor tyrosine kinases