Cancer Cell & Microenvironment 2014; 1: e420. doi: 10.14800/ccm.420; © 2014 by Sari Trangle Schokoroy, et al. http://www.smartscitech.com/index.php/ccm Page 1 of 4 Breaking the malignant triangle in glioblastoma - ErbB1/nucleoin/Ras Sari Trangle Schokoroy 1 , Yona Goldshmit 1,2 , Yoel Kloog 1 , Ronit Pinkas-Kramarski 1 1 Department of Neurobiology, Tel-Aviv University, Ramat-Aviv, Israel 2 Australian Regenerative Medicine Institute, Monash University, Australia Correspondence: Ronit Pinkas-Kramarski E-mail: lironit@post.tau.ac.il Received: November 12, 2014 Published online: December 25, 2014 Glioblastoma is one of the most malignant tumors in humans, with poor diagnosis and a low survival rate. These tumors overexpress the ErbB1 receptor and have high levels of cell surface nucleolin, which serves as an indicator for disease grade. We have previously identified a crosstalk between three oncogenes: ErbB1, Ras and nucleolin. This lead us to suggest a combined treatment using FTS, to target Ras protein, and GroA, to target cell surface nucleolin, in order to break this malignant synergy. Here we review our recent findings and suggest a model explaining drugs activities: inhibition of Ras using FTS mainly reduces cell viability and motility and inhibition of nucleolin using GroA reduces the cell proliferation. The combined treatment has a more pronounced effect on glioblastoma growth. Keywords: Glionlastoma; ErbB1; Ras; nucleolin; FTS; GroA To cite this article: Sari Trangle,Schokoroy, et al. Breaking the malignant triangle in glioblastoma - ErbB1/nucleoin/Ras. Can Cell Microenviron 2014; 1: e420. doi: 10.14800/ccm.420. Signal transduction pathways are at the center of a diverse range of essential biological processes within cells, including proliferation, differentiation, morphogenesis, and cell death [1, 2] . Cells sense the environment through several classes of receptors, which bind growth factors and hormones [3, 4] . The ErbB subfamily of receptors belongs to the receptor tyrosine kinases family (RTKs), which lies at the head of a complex signal transduction cascade. ErbB1 also known as epidermal growth factor receptor (EGFR) is one of the four ErbB subfamily members. Deregulation of these receptors' expression and their growth factors might lead to excessive cell proliferation, survival, and eventually, to the development of malignancy. The majority of tumors originating in the central nervous system are gliomas. Gliomas are a heterogeneous group of neoplasms that overexpress the EGFR receptor [5, 6] . One of the most severe subtypes of gliomas is the glioblastoma. Despite notable recent achievements in oncology, malignant glioblastoma multiform (GBM) has a 14 months prognosis after diagnosis, posing a challenge to researchers [7] . Nucleolin is a multifunctional, ubiquitously expressed phosphoprotein, whose expression often correlates with increased cellular proliferation [7-9] . Nucleolin is localized predominantly in the nucleoli, but it transports between the nucleus and cytoplasm, and it can be also found on the cell surface [8, 10, 11] . Cytoplasmic and cell surface nucleolin was found to be highest in tumors and other rapidly dividing cells and consequently its expression has become an indicator in studies of cell proliferation and terming the malignancy grade of the glioblastoma [8, 12-14] . Expression of extensive levels of nucleolin has been demonstrated in glioblastoma cell lines and primary astrocytoma cells, contrary to astrocytes in normal human brain [15] . It was previously shown that inhibition nucleolin at the cell-surface and blocking its activities, suppresses growth of glioblastoma cell RESEARCH HIGHLIGHT