Abstract
Simple SummaryIQ motif-containing GTPase-activating protein 1 (IQGAP1) is a signal scaffolding protein that regulates a range of cellular activities by facilitating signal transduction in cells. IQGAP1 is involved in many cancer-related activities, such as proliferation, apoptosis, migration, invasion and metastases. In this article, we review the different pathways regulated by IQGAP1 during cancer development, and the role of IQGAP1 in different types of cancer, including cancers of the head and neck, breast, pancreas, liver, colorectal, stomach, and ovary. We also discuss IQGAP1′s regulation of the immune system, which is of importance to cancer progression. This review highlights the significant roles of IQGAP1 in cancer and provides a rationale for pursuing IQGAP1 as a drug target for developing novel cancer therapies.Scaffolding proteins can play important roles in cell signaling transduction. IQ motif-containing GTPase-activating protein 1 (IQGAP1) influences many cellular activities by scaffolding multiple key signaling pathways, including ones involved in carcinogenesis. Two decades of studies provide evidence that IQGAP1 plays an essential role in promoting cancer development. IQGAP1 is overexpressed in many types of cancer, and its overexpression in cancer is associated with lower survival of the cancer patient. Here, we provide a comprehensive review of the literature regarding the oncogenic roles of IQGAP1. We start by describing the major cancer-related signaling pathways scaffolded by IQGAP1 and their associated cellular activities. We then describe clinical and molecular evidence for the contribution of IQGAP1 in different types of cancers. In the end, we review recent evidence implicating IQGAP1 in tumor-related immune responses. Given the critical role of IQGAP1 in carcinoma development, anti-tumor therapies targeting IQGAP1 or its associated signaling pathways could be beneficial for patients with many types of cancer.
Highlights
IQ motif-containing GTPase-activating protein 1 (IQGAP1) belongs to the IQGAP protein family, which is evolutionarily conserved among eukaryotes [1,2]
head and neck squamous cell carcinoma (HNSCC) samples, we found that high levels of IQGAP1 correlate positively with high levels of PI3K signaling, further supporting the association between IQGAP1 and PI3K signaling in HNSCCs [51]
Evidence has emerged on new roles played by IQGAP1 in signal transduction in carcinogenesis
Summary
IQ motif-containing GTPase-activating protein 1 (IQGAP1) belongs to the IQGAP protein family, which is evolutionarily conserved among eukaryotes [1,2]. IQGAP1 is a large protein with a size of 190 kDa (1657 amino acids (aa)) that is ubiquitously expressed [3] This protein has five main domains through which it binds to other proteins: a calponin-homology domain (CHD, 44–159 aa), a poly-proline protein–protein domain (WW, 681–710 aa), a domain containing four IQ-motif (IQ, 745–864 aa), a Ras GAP-related domain (GRD, 1004–1237 aa), and a Ras GAP C-terminal domain (RGCT 1276–1657 aa) [5]. We describe the different oncogenic pathways affected by IQGAP1, summarize the role of IQGAP1 in different types of cancer, and discuss the emerging evidence of IQGAP1 in regulating tumor immunology
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