IQGAP1-siRNA inhibits proliferation and metastasis of U251 and U373 glioma cell lines

Diao, Bo; Liu, Ying; Zhang, Yi; Yu, Jing; Xie, Jun; Xu, Guohai

doi:10.3892/mmr.2017.6257

Cited by 22 publications

(15 citation statements)

References 41 publications

(54 reference statements)

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“…In human embryonic kidney cells, HEK-293, it was proven that the MEK/ERK signaling pathway interacts with Nrf2 through IQ Motif Containing GTPase Activating Protein 1 (IQGAP1) [106]. IQGAP1 functions as a tumor-promoting protein in breast cancer [107], glioma [108], and ovarian cancer [109].…”

Section: The Interplay Between Nrf2 and Other Signaling Pathwaysmentioning

confidence: 99%

The Role of Nrf2 Activity in Cancer Development and Progression

Zimța

Cenariu

Irimie

et al. 2019

Cancers

194

135

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Nrf2 is a transcription factor that stimulates the expression of genes which have antioxidant response element-like sequences in their promoter. Nrf2 is a cellular protector, and this principle applies to both normal cells and malignant cells. While healthy cells are protected from DNA damage induced by reactive oxygen species, malignant cells are defended against chemo- or radiotherapy. Through our literature search, we found that Nrf2 activates several oncogenes unrelated to the antioxidant activity, such as Matrix metallopeptidase 9 (MMP-9), B-cell lymphoma 2 (BCL-2), B-cell lymphoma-extra large (BCL-xL), Tumour Necrosis Factor α (TNF-α), and Vascular endothelial growth factor A (VEGF-A). We also did a brief analysis of The Cancer Genome Atlas (TCGA) data of lung adenocarcinoma concerning the effects of radiation therapy and found that the therapy-induced Nrf2 activation is not universal. For instance, in the case of recurrent disease and radiotherapy, we observed that, for the majority of Nrf2-targeted genes, there is no change in expression level. This proves that the universal, axiomatic rationale that Nrf2 is activated as a response to chemo- and radiation therapy is wrong, and that each scenario should be carefully evaluated with the help of Nrf2-targeted genes. Moreover, there were nine genes involved in lipid peroxidation, which showed underexpression in the case of new radiation therapy: ADH1A, ALDH3A1, ALDH3A2, ADH1B, GPX2, ADH1C, ALDH6A1, AKR1C3, and NQO1. This may relate to the fact that, while some studies reported the co-activation of Nrf2 and other oncogenic signaling pathways such as Phosphoinositide 3-kinases (PI3K), mitogen-activated protein kinase (MAPK), and Notch1, other reported the inverse correlation between Nrf2 and the tumor-promoter Transcription Factor (TF), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Lastly, Nrf2 establishes its activity through interactions at multiple levels with various microRNAs. MiR-155, miR-144, miR-28, miR-365-1, miR-93, miR-153, miR-27a, miR-142, miR-29-b1, miR-340, and miR-34a, either through direct repression of Nrf2 messenger RNA (mRNA) in a Kelch-like ECH-associated protein 1 (Keap1)-independent manner or by enhancing the Keap1 cellular level, inhibit the Nrf2 activity. Keap1–Nrf2 interaction leads to the repression of miR-181c, which is involved in the Nuclear factor kappa light chain enhancer of activated B cells (NF-κB) signaling pathway. Nrf2’s role in cancer prevention, diagnosis, prognosis, and therapy is still in its infancy, and the future strategic planning of Nrf2-based oncological approaches should also consider the complex interaction between Nrf2 and its various activators and inhibitors.

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Section: The Interplay Between Nrf2 and Other Signaling Pathwaysmentioning

confidence: 99%

The Role of Nrf2 Activity in Cancer Development and Progression

Zimța

Cenariu

Irimie

et al. 2019

Cancers

194

135

View full text Add to dashboard Cite

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“…One such protein is IQGAP1, a scaffold protein which binds both Rac1 and Cdc42 and helps reorganize actin cytoskeletal structures [76]. Knockdown of IQGAP1 inhibits both Rac1-and Cdc42-mediated migration and invasion of glioma cells and leads to the suppression of several other components of the invasion process such as MMPs [77]. It is therefore not surprising that in addition to Cdc42, high levels of proteins that interact with Cdc42 like 3 Analytical Cellular Pathology IQGAP1 are correlated with poor survival of patients with glioma [78].…”

Section: Altered Rho-gtpasementioning

confidence: 99%

The Role of Rho GTPases in Motility and Invasion of Glioblastoma Cells

Al-Koussa

Atat

Jaafar

et al. 2020

Analytical Cellular Pathology

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Astrocytomas are primary malignant brain tumors that originate from astrocytes. Grade IV astrocytoma or glioblastoma is a highly invasive tumor that occur within the brain parenchyma. The Rho family of small GTPases, which includes Rac1, Cdc42, and RhoA, is an important family whose members are key regulators of the invasion and migration of glioblastoma cells. In this review, we describe the role played by the Rho family of GTPases in the regulation of the invasion and migration of glioblastoma cells. Specifically, we focus on the role played by RhoA, Rac1, RhoG, and Cdc42 in cell migration through rearrangement of actin cytoskeleton, cell adhesion, and invasion. Finally, we highlight the importance of potentially targeting Rho GTPases in the treatment of glioblastoma.

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“…Dysregulation of the PI3K/Akt signaling pathway have been linked to enhanced cell migration and motility in various diseases such as cancer [1,2]. IQGAP1 is upregulated in several different types of cancers [52], including hepatocellular [53,54], prostate [55], glioma [56] and breast [57] cancers. In most studies, perturbing IQGAP1 levels by upregulation or downregulation has a corresponding effect on cell migration in a variety of normal and cancer cell lines [55][56][57][58].…”

Section: Discussionmentioning

confidence: 99%

IQGAP1 connects phosphoinositide signaling to cytoskeletal reorganization

Yerramilli

Ross

Lindberg³

et al. 2019

Preprint

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IQGAP1 is a multi-domain protein that acts as a scaffold for multiple signaling pathways. IQGAP1 generates the lipid messenger PI(3,4,5)P 3 by scaffolding the phosphoinositide kinases PIPKIs and PI3K.The dynamics of this scaffolding protein complex in intact, living cells are unknown. Here, we delineate the role of IQGAP1 in PI(3,4,5)P 3 -mediated signaling in live cells under basal and stimulated conditions using fluorescence lifetime imaging microscopy. We demonstrate that IQGAP1 interacts strongly with PIPKIγ at intracellular entities and on the plasma membrane, and scaffolds PI3K and PIPKIγ in response to physiological changes. Additionally, we show that IQGAP1 scaffolds phosphoinositides with PI3K, PIPKIγ and EGFR, and forms clusters upon cell stimulation with epidermal growth factor. Importantly, we show that IQGAP1 connects PI(3,4,5)P 3 -mediated signaling and cytoskeletal signaling pathways by binding PIPKIγ in proximity of the cytoskeletal proteins talin and Cdc42. Our results support a model in which IQGAP1 mediates crosstalk between phosphoinositide signaling and the cytoskeleton to promote directed cell movement. IQGAP1 connects PI signaling to cytoskeletal reorganization

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IQGAP1-siRNA inhibits proliferation and metastasis of U251 and U373 glioma cell lines

Cited by 22 publications

References 41 publications

The Role of Nrf2 Activity in Cancer Development and Progression

The Role of Nrf2 Activity in Cancer Development and Progression

The Role of Rho GTPases in Motility and Invasion of Glioblastoma Cells

IQGAP1 connects phosphoinositide signaling to cytoskeletal reorganization

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