Role of IQGAP3 in metastasis and epithelial–mesenchymal transition in human hepatocellular carcinoma

Shi, Yongjie; Qin, Nan; Zhou, Qiang; Chen, Yanqiu; Huang, Sicong; Chen, Bo; Shen, Gang; Jia, Hongyun

doi:10.1186/s12967-017-1275-8

Cited by 52 publications

(54 citation statements)

References 42 publications

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“…Recently, IQGAP3 expression was found to be related to clinical stage and was an independent prognostic classifier of gastric cancer patients: IQGAP3 knockdown reduced both the number and size of the spheres formed by the gastric cancer cell line MKN-74 and inhibited the phosphorylation of Akt and Erk1/2[11]. In hepatocellular carcinoma, IQGAP3 was reported to function as an important regulator of epithelial-mesenchymal transition (EMT) and metastasis by activating the transforming growth factor (TGF)-β signaling pathway[9]. Regarding breast cancer, IQGAP3 knockdown by RNA interference inhibited cell proliferation and invasion in two breast carcinoma cell-lines[12].…”

Section: Introductionmentioning

confidence: 99%

IQGAP3 Overexpression Correlates with Poor Prognosis and Radiation Therapy Resistance in Breast Cancer

Hua

Long

zhang

et al. 2018

Preprint

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Background: IQ motif-containing GTPase activating 24 protein 3 (IQGAP3), the latest found protein of IQGAP family, 25 may act as a crucial factor in the process of cancer development 26 and progression; however, its clinical value in breast cancer 27 remains unestablished so far. Our team explored the correlation 28 between IQGAP3 expression profile and the clinicopathological 29 features in breast cancer. Methods: IQGAP3 levels in breast 30 cancer cell lines and tumor tissues were detected by real-time 31 PCR and western blotting and compared to the normal control 32 groups. Protein expression of IQGAP3 was evaluated 33 immunohistochemically in specimens (archived paraffin 34 embedded) of 257 breast cancer patients. We also analyze the 35 association between IQGAP3 expression and the clinical 36 characters and prognosis. The relationship between IQGAP3 37 expression and sensitivity to radiation therapy was determined 38 by subgroup analysis. Results: There was significant 39 upregulation of IQGAP3 in breast cancer cell lines and human 40 tumor tissues at both the mRNA and protein level compared to 41 the normal ones. In addition, 110/257 (42.8%) of archived 42 paraffin embedded breast cancer specimens had high protein 43 expression of IQGAP3. High expression of IQGAP3 was 44 significantly related to clinical stage (P=0.001), T category 45 (P=0.002), N category (P=0.001), locoregional 46 recurrence(P=0.002), distant metastasis (P=0.001), and vital 47 status (P=0.001). Univariate and multivariate statistical analysis 48showed that IQGAP3 was an independent prognostic factor of 49 the whole cohort breast cancer patients (P=0.003, P=0.001). 50Subgroup analysis revealed IQGAP3 expression correlates with 51 radiation therapy resistance and was also an independent 52 predictor for radiation therapy outcome. Conclusions: Our 53 findings suggest that high IQGAP3 expression predicts poor 54 prognosis and radiation therapy resistance in breast cancer. In 55 addition, IQGAP3 may be a reliable novel biomarker to provide 56 personalized prognostication and identify patients who can 57 profit from more aggressive RT regimen for improving the 58 survival of breast cancer patients. 59 1. Introduction 62 Breast cancer is the most frequent malignancy in women and the 63 second leading cause of cancer-related deaths worldwide[1]. Radiation 64 therapy (RT) is an indispensable part of the systemic therapeutic regimen 65 of breast cancer. Despite great progress in RT over recent years, 66 locoregional recurrence and distant metastasis after RT remain key 67 problems decreasing the survival of breast cancer patients [2]. 68 Locoregional recurrence results from the presence or evolution of 69 radioresistant tumor cells for which standard fractionated RT doses are 70 sublethal[3]. Currently, there is a dearth of clinically available 71 predictive biomarkers to indicate the optimal radiation dosing in breast 72 cancer, which leads to suboptimal treatment of these patients[4]. 73 Therefore, further researches to identify novel biomarkers a...

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Section: Introductionmentioning

confidence: 99%

IQGAP3 Overexpression Correlates with Poor Prognosis and Radiation Therapy Resistance in Breast Cancer

Hua

Long

zhang

et al. 2018

Preprint

View full text Add to dashboard Cite

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“…IQGAP3 has also been associated with markers of apoptosis and metastasis. Shi and colleagues have shown that epithelial-mesenchymal transition (EMT) markers including e-cadherin, fibronectin, vimentin, n-cadherin are overexpressed in HCC cells with up-regulation of IQGAP3, while knockdown of IQGAP3 showed the reduction of the above markers [45]. Furthermore, IQGAP3 functions as an important regulator of metastasis and EMT by constitutively activating the TGF-beta signaling pathway; hence, it may also play some roles in promoting cancer stemness through regulation of tumor microenvironment [46].…”

Section: Discussionmentioning

confidence: 99%

Enhancement of Migration and Invasion of Gastric Cancer Cells by IQGAP3

et al. 2020

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Although gastric cancer is one of the most common causes of cancer death in the world, mechanisms underlying this type of tumor have not been fully understood. In this study, we found that IQGAP3, a member of the IQGAP gene family, was significantly up-regulated in human gastric cancer starting from the early stages of tumor progression. Overexpression of IQGAP3 in 293T and NIH3T3 cells, which have no endogenous IQGAP3 expression, resulted in morphological change with multiple dendritic-like protrusions and enhanced migration. Overexpression of IQGAP3 also led to reduced cell–cell adhesion in 293T cells, likely as a result of its interactions with e-cadherin or β-catenin proteins. Additionally, IQGAP3 accumulated along the leading edge of migrating cells and at the cleavage furrow of dividing cells. In contrast, suppression of IQGAP3 by short-interfering RNA (siRNA) markedly reduced invasion and anchorage-independent growth of MKN1 and TMK-1 gastric cancer cells. We further confirmed that IQGAP3 interacted with Rho family GTPases, and had an important role in cytokinesis. Taken together, we demonstrated that IQGAP3 plays critical roles in migration and invasion of human gastric cancer cells, and regulates cytoskeletal remodeling, cell migration and adhesion. These findings may open a new avenue for the diagnosis and treatment of gastric cancer.

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“…PTTG1 has been reported to be associated with poor prognosis and angiogenesis in HCC (35). IQGAP3 functions as a potential oncogene by activating metastasis and EMT in HCC (36). CDKN3 has been correlated with poor tumor differentiation and advanced tumor stage by promoting cell proliferation in HCC (37).…”

Section: Discussionmentioning

confidence: 99%

Development of a Prognostic Gene Signature For Hepatocellular Carcinoma

Luo

et al. 2020

Preprint

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Background: Accurate prediction of overall survival is important for prognosis and the assignment of appropriate personalized clinical treatment in hepatocellular carcinoma (HCC) patients. The aim of the present study was to establish an optimal gene model for the independent prediction of prognosis associated with common clinical patterns.Methods: Gene expression profiles and the corresponding clinical information of the LIHC cohort were obtained from The Cancer Genome Atlas. Differentially expressed genes were found using the R package “limma”. Subsequently, a prognostic gene signature was developed using the LASSO Cox regression model. Kaplan–Meier, log-rank, and receiver operating characteristic (ROC) analyses were performed to verify the predictive accuracy of the prognostic model. Finally, a nomogram and calibration plot were created using the “rms” package.Results: Differentially expressed genes were screened with threshold criteria (FDR < 0.01 and |log FC|>3) and 563 differentially expressed genes were obtained, including 448 downregulated and 115 upregulated genes. Using the LASSO Cox regression model, a prognostic gene signature was developed based on nine genes,IQGAP3, BIRC5, PTTG1, STC2, CDKN3, PBK, EXO1, NEIL3, and HOXD9, the expression levels of which were quantitated using RT-qPCR. According to the risk scores, patients were separated into high-risk and low-risk groups. Patients with lower risk scores generally had a better survival rate than those with higher risk scores. The mortality rate in the high-risk group was 42.02%, while that in the low-risk group was 12.50%. Results of the log-rank test showed significant differences in mortality between the two groups (HR: 4.86; 95% CI: 2.72–8.69; P = 1.01E-08). Subsequently, we assessed the prognostic accuracy of the gene signature using an ROC curve and the results show good sensitivity and specificity, with an average area under the curve (AUC) of 0.81 at 5 years (P < 0.01). Following multivariate adjustment for conventional clinical patterns, the prognostic gene signature remained a powerful and independent factor (HR: 4.70; 95% CI: 2.61–8.38; P = 2.06E-07), confirming its robust predictive ability of overall survival in HCC patients. Finally, a nomogram was established based on the gene signature and four clinicopathological features, which demonstrated an advantageous discriminating ability with the potential to facilitate clinical decision-making in HCC.Conclusion: Our prognostic gene signature can be used as a combined biomarker for the independent prediction of overall survival in HCC patients. Moreover, we created a nomogram that can be used to infer prognosis and aid individualized decisions regarding treatment and surveillance.

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Role of IQGAP3 in metastasis and epithelial–mesenchymal transition in human hepatocellular carcinoma

Cited by 52 publications

References 42 publications

IQGAP3 Overexpression Correlates with Poor Prognosis and Radiation Therapy Resistance in Breast Cancer

IQGAP3 Overexpression Correlates with Poor Prognosis and Radiation Therapy Resistance in Breast Cancer

Enhancement of Migration and Invasion of Gastric Cancer Cells by IQGAP3

Development of a Prognostic Gene Signature For Hepatocellular Carcinoma

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