%0 Journal Article
%T The Role of Semaphorins and Their Receptors in Gliomas
%A Janice Wai Sze Law
%A Alan Yiu Wah Lee
%J Journal of Signal Transduction
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/902854
%X Gliomas are the most common tumor in the central nervous system. High-grade glioblastomas are characterized by their high invasiveness and resistance to radiotherapy, leading to high recurrence rate and short median survival despite radical surgical resection. Characterizations of gliomas at molecular level have revealed aberrations of various growth factor receptors, receptor tyrosine kinases, and tumor suppressor genes that lead to deregulation of multiple signaling pathways, thereby contributing to abnormal proliferation, invasion, and resistance to apoptosis in cancer cells. Recently, accumulating evidence points to the emerging role of axon guidance molecules in glioma progression. Notably, many signaling events harnessed by guidance molecules to regulate cell migration and axon navigation during development are also found to be involved in the modulation of deregulated pathways in gliomas. This paper focused on the signalings triggered by the guidance molecule semaphorins and their receptors plexins and neuropilins, and how their crosstalk with oncogenic pathways in gliomas might modulate cancer progression. The emerging role of semaphorins and plexins as tumor suppressors or oncogenes is also discussed. 1. Introduction Gliomas are the most common tumor in the central nervous system, with an incidence rate of 5 to 10 per 100,000 for the malignant form [1]. Based on their histological characteristics and expression of lineage markers, gliomas can be classified into astrocytoma, oligodendroglioma, and ependymoma [2]. Astrocytomas account for 60% of all primary brain tumors and the World Health Organization (WHO) classification system grades them on a scale of I to IV according to their increasing degree of malignancy [3]. Among them, Grade IV is one of the most highly invasive types of tumor [4], characterized by microvascular proliferation. Its aggressive infiltrative growth leads to an extremely high recurrence rate within a short period of time even after radical surgical resection. Worse still, many glioblastomas are found to be resistant to chemo- or radiotherapy due to DNA repair by the protein O6-methylguanine-methyltransferase (MGMT) and impaired apoptotic pathways. Median survival after initial diagnosis is therefore currently only around 12 to 18 months [5]. This apparently calls for a more thorough understanding of the pathoetiology at both cellular and molecular level to provide insight into the devise of novel and effective therapeutic treatments. This paper revisits the biological features of various genetic pathways deregulated in
%U http://www.hindawi.com/journals/jst/2012/902854/