Grb2 signaling in cell motility and cancer

Abstract

Metastasis is the primary cause of death in most human cancers, and understanding the molecular mechanisms underpinning this multistep process is fundamental to identifying novel molecular targets and developing more effective therapies. Growth Factor Receptor-bound protein 2 (Grb2) is a key molecule in intracellular signal transduction, linking activated cell surface receptors to downstream targets by binding to specific phosphotyrosine-containing and proline-rich sequence motifs. Grb2 signaling is critical for cell cycle progression and actin-based cell motility, and consequently, more complex processes such as epithelial morphogenesis, angiogenesis and vasculogenesis. These important functions make Grb2 a logical therapeutic target for strategies designed to prevent the spread of solid tumors through local invasion and metastasis. Here we review the role of Grb2 in cancer and specifically in metastasis-related processes, and summarize briefly the development of anti-cancer therapeutics selectively targeting this important adapter protein.

Specific Alterations of MicroRNA Transcriptome and Global Network Structure in Colorectal Carcinoma after Cetuximab Treatment

“…Unsurprisingly, the 4 networks of differentially expressed miRNA targets and their first interactors are centered on the same hubs, EEF1A1, GRB2, and UBC. Although the role of EEF1A1 in CRC remains unsatisfactorily characterized, the involvement of GRB2 and UBC in the regulation of EGFR pathway has been proved (22,44). In particular, GRB2 is a critical link between cell surface growth factor receptors and the RAS signaling pathway, participating in EGFR internalization and its subsequent ubiquitylation (44).…”

“…Although the role of EEF1A1 in CRC remains unsatisfactorily characterized, the involvement of GRB2 and UBC in the regulation of EGFR pathway has been proved (22,44). In particular, GRB2 is a critical link between cell surface growth factor receptors and the RAS signaling pathway, participating in EGFR internalization and its subsequent ubiquitylation (44). Moreover, the ubiquitin complex regulates other key molecules in CRC carcinogenesis and components of the K-ras pathways.…”

MiRNA-29a regulates the expression of numerous proteins and reduces the invasiveness and proliferation of human carcinoma cell lines

“…17,18 GRB2 (growth factor receptor-bound protein 2) is a crucial adaptor protein that mediates cell signalling from the surface membrane receptors to their downstream targets and indeed is a current target for the development of anticancer therapeutics. 19,20 It was interesting to observe that, despite being identified in the proteomic analysis, subsequent qPCR analyses of both miR-29a-transfected and untransfected cells indicated extremely low levels of GRB2 transcript (data not shown). Several peroxiredoxin family members were identified as being down-regulated in response to miR-29a transfection supporting several reports correlating their expression with cancer development and recurrence.…”

Basic study on SH2 domain of Grb2 as a molecular probe for detection of RTK activation

“…The importance of Grb2 signaling in cell cycle progression and cell motility is now increasingly recognized (35). Although only the activation of EGFR was examined in this study, it would be interesting to explore the possibility to capture the activation of other signaling pathways going through Grb2 using TSF.…”