2015
DOI: 10.18632/aging.100781
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Abstract: Most common diseases, e.g., cancer are driven by not one, but multiple cell surface receptors that trigger and sustain a pathologic signaling network. The largest fraction of therapeutic agents that target individual receptors/pathways eventually fail due to the emergence of compensatory mechanisms that reestablish the pathologic network. Recently, a rapidly emerging paradigm has revealed GIV/Girdin as a central platform for receptor cross-talk which integrates signals downstream of a myriad of cell surface re… Show more

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Cited by 32 publications
(52 citation statements)
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References 61 publications
(28 reference statements)
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“…GIV is a multifunctional protein involved in cancer, angiogenesis, fibrosis, and neurodevelopment among others (18,19). The best characterized cellular function of GIV is as an enhancer of cell migration, which underlies its role as a prometastatic protein in cancer (20 -23).…”
mentioning
confidence: 99%
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“…GIV is a multifunctional protein involved in cancer, angiogenesis, fibrosis, and neurodevelopment among others (18,19). The best characterized cellular function of GIV is as an enhancer of cell migration, which underlies its role as a prometastatic protein in cancer (20 -23).…”
mentioning
confidence: 99%
“…The best characterized cellular function of GIV is as an enhancer of cell migration, which underlies its role as a prometastatic protein in cancer (20 -23). Previous work has established that GIV is overexpressed during cancer metastasis (24 -31) and promotes PI3K-Akt signaling downstream of different classes of receptors such as GPCRs and RTKs (19,24,25,32). Our recent work on integrin signaling (17) has expanded the repertoire of receptors that utilize GIV as a signaling platform to enhance PI3K signaling and promote tumor cell invasiveness.…”
mentioning
confidence: 99%
“…Based on the broad range of receptor-initiated signals that converge on GIV and the variety of signaling pathways within ‘disease networks’ that are modulated via GIV’s GEF function [summarized in (8)], it is predicted that disrupting the GIV•Gαi interface will be the most specific and effective approach for modulating multi-receptor signaling via GIV. Such an approach is expected to have the tremendous advantage of allowing ‘network-based therapy’ irrespective of the receptor of origin (85). Recently, we showed just that in a proof-of-concept study using cell-permeable peptides (68).…”
Section: Therapeutic Potential Of Tyrosine-based G Protein Signalingmentioning
confidence: 99%
“…For example, in the context of cancer progression, others and us have reported that expression of GIV at high levels correlates with tumor aggressiveness and poor survival across a variety of solid tumors (85). A consensus has emerged that patients with GIV-positive tumors are at highest risk for cancer progression and may maximally benefit from systemic chemotherapy.…”
Section: Tyrosine-based G Protein Signaling Offers a Unique Opportunimentioning
confidence: 99%
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