MTA1 promotes viability and motility in nasopharyngeal carcinoma by modulating IQGAP1 expression

Lu, Baocai; Lian, Rong; Wu, Zhiyan; Miao, Wenjie; Li, Xiao; Jin, Li; Shi, Yongjuan; Yu, Wenfa

doi:10.1002/jcb.26494

Cited by 8 publications

(6 citation statements)

References 35 publications

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“…IQGAP1 binds directly to EGFR and facilitates its activation, and scaffolds components of the downstream PI3K signaling pathway [14,48]. Levels of IQGAP1 are often upregulated in the tumors of HNSCC patients [67,68,[92][93][94]. Overexpression of IQGAP1 correlates with poorer HNSCC patient survival [51,67].…”

Section: Iqgap1 In Head and Neck Cancermentioning

confidence: 99%

“…IQGAP1 contributes to esophageal cancer by promoting the angiogenesis process through AKT and ERK activation [95]. In nasopharyngeal cancer, metastasis-associated protein 1 (MTA1) regulates IQGAP1 expression and promotes cell proliferation and motility [92]. Inhibition of MTA1 downregulates PI3K signaling in a nasopharyngeal cancer cell line [92].…”

Section: Iqgap1 In Head and Neck Cancermentioning

confidence: 99%

“…In nasopharyngeal cancer, metastasis-associated protein 1 (MTA1) regulates IQGAP1 expression and promotes cell proliferation and motility [92]. Inhibition of MTA1 downregulates PI3K signaling in a nasopharyngeal cancer cell line [92]. Targeting the IQGAP1-mediated PI3K signaling using the IQ3 peptide also inhibits human HNSCC cell survival, proliferation, migration, and invasion, indicating the importance of IQGAP1-mediated PI3K signaling in HNSCC cell lines [50,51].…”

Section: Iqgap1 In Head and Neck Cancermentioning

confidence: 99%

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Role of IQGAP1 in Carcinogenesis

Tao

Lambert

2021

Cancers

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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.

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Section: Iqgap1 In Head and Neck Cancermentioning

confidence: 99%

Section: Iqgap1 In Head and Neck Cancermentioning

confidence: 99%

Section: Iqgap1 In Head and Neck Cancermentioning

confidence: 99%

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Role of IQGAP1 in Carcinogenesis

Tao

Lambert

2021

Cancers

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“…IQGAP1 is overexpressed in many human cancers (12,20,21,33,34). We therefore looked at levels of IQGAP1 protein in our 4NQOinduced HNC model by immunofluorescence.…”

Section: Iqgap1 Protein Levels Are Upregulated In Hncmentioning

confidence: 99%

A PI3K/AKT Scaffolding Protein, IQ Motif–Containing GTPase Associating Protein 1 (IQGAP1), Promotes Head and Neck Carcinogenesis

Tao

Choi

Buehler

et al. 2020

Clinical Cancer Research

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Purpose: Head and neck cancer (HNC) is the sixth most common cancer worldwide with a 5-year survival rate of less than 50%. The PI3K/AKT/mTOR signaling pathway is frequently implicated in HNC. Recently, IQ motif-containing GTPaseactivating protein 1 (IQGAP1) was discovered to scaffold the PI3K/AKT signaling pathway. IQGAP1 gene expression is increased in HNC, raising the hypothesis that IQGAP1 contributes to HNC.Experimental Design: We performed a combination of in vitro studies using human cancer cell lines treated with a cell-permeable peptide that interferes with IQGAP1's ability to bind to PI3K, and in vivo studies utilizing mice genetically knocked out for the Iqgap1 (Iqgap1 À/À ). In vivo EGF stimulation assays were used to evaluate PI3K signaling. To study the role of IQGAP1 in HNC, we used a well-validated mouse model that drives HNC via a synthetic oral carcinogen, 4-nitroquinoline 1-oxide (4NQO).Results: IQGAP1 is necessary for efficient PI3K signaling in vitro and in vivo. Disruption of IQGAP1-scaffolded PI3K/AKT signaling reduced HNC cell survival. Iqgap1 À/À mice had significantly lower cancer incidences, lesser disease severity, and fewer cancer foci. IQGAP1 protein levels were increased in HNC arising in Iqgap1 þ/þ mice. The level of PI3K signaling in 4NQO-induced HNC arising in Iqgap1 À/À mice was significantly reduced, consistent with the hypothesis that IQGAP1 contributes to HNC at least partly through PI3K signaling. High IQGAP1 expression correlated with reduced survival, and high pS6 levels correlated with high IQGAP1 levels in patients with HNC.Conclusions: These data demonstrate that IQGAP1 contributes to head and neck carcinogenesis.

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“…IQGAP1 is overexpressed in many human cancers [15,18,26,27] . We therefore looked at levels of IQGAP1 protein in our 4NQO-induced HNSCC model.…”

Section: Iqgap1 Protein Levels Are Upregulated In Hnsccmentioning

confidence: 99%

Role of IQGAP1 in Head and Neck Carcinogenesis

Tao¹,

Choi²,

Buehler³

et al. 2018

Preprint

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Head and neck squamous cell carcinoma (HNSCC) is a common cancer in humans.Phosphoinositide 3-kinase (PI3K)/AKT signaling, along with its downstream effector mTOR, is one of the most frequently altered pathways in HNSCC, and is downstream of growth factor signaling including that mediated by epidermal growth factor receptor (EGFR), which is also commonly upregulated in HNSCC. Recently, IQ motif-containing GTPase activation protein 1 (IQGAP1) has been reported to function as a scaffold for the enzymes involved in the PI3K/AKT signaling pathway. Iqgap1 gene expression is increased in human HNSCCs, raising the hypothesis that it acts as an oncogene in this cancer. Whether IQGAP1 is necessary for HNSCC development as well as what is its underlying mechanism are both unknown. Here we report on the role of IQGAP1 in HNSCC by performing a combination of in vitro studies using human cancer cell lines, and in vivo studies using a well-validated preclinical mouse model for HNSCC that is known to depend upon EGFR signaling. Cells knocked out for IQGAP1 lost AKT signaling. Disruption of IQGAP1-scaffolded PI3K/AKT signaling using a peptide that interferes with the ability of IQGAP1 to bind to PI3K reduced HNSCC cell survival. In vivo studies utilizing Iqgap1-null (Iqgap1

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MTA1 promotes viability and motility in nasopharyngeal carcinoma by modulating IQGAP1 expression

Cited by 8 publications

References 35 publications

Role of IQGAP1 in Carcinogenesis

Role of IQGAP1 in Carcinogenesis

A PI3K/AKT Scaffolding Protein, IQ Motif–Containing GTPase Associating Protein 1 (IQGAP1), Promotes Head and Neck Carcinogenesis

Role of IQGAP1 in Head and Neck Carcinogenesis

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