Eps15 homology domain 1 promotes the evolution of papillary thyroid cancer by regulating endocytotic recycling of epidermal growth factor receptor

Purpose. The incidence of papillary thyroid cancer (PTC) is increasing, and traditional diagnostic methods are unsatisfactory. Therefore, identifying novel prognostic markers is very important. ciRS-7 has been found to play an important role in many cancers, but its role in PTC has not been reported. This study was performed to evaluate the biological role and mechanism of ciRS-7 in PTC. Material and Methods. The expression of ciRS-7 in PTC tissues and the matched adjacent tissues was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The PTC cell lines (TPC-1 and BCPAP) were used to evaluate the role of ciRS-7. ciRS-7-siRNA and overexpression plasmid were constructed and transfected into PTC cells. A CCK-8 assay and colony formation assay were performed to explore the effects of ciRS-7 on cell proliferation. Annexin V/PI staining and FACS detection were used to detect cell apoptosis. Wound healing assay was performed to detect cell migration. A transwell assay was conducted to explore the effects of ciRS-7 on invasion and migration. Western blotting was performed to evaluate protein expression. The luciferase reporter system was used to determine the underlying mechanism of miR-7. Result. ciRS-7 was highly expressed in PTC tissues and cell lines compared with the corresponding controls. In vitro study showed that ciRS-7 silencing suppressed proliferation, migration, and invasion of TPC-1 and BCPAP. Mechanistically, the effects of ciRS-7 on invasion and migration may be related to epithelial-mesenchymal transition (EMT). ciRS-7 silencing could attenuate effects on PTC cells induced by miR-7 knockdown. Epidermal growth factor receptor (EGFR), which was demonstrated to be a target of miR-7, decreased significantly in ciRS-7-siRNA PTC cells. Overexpression of EGFR also attenuated effects of PTC cells induced by silencing ciRS-7. Conclusion. ciRS-7 was significantly upregulated in PTC tissues, and it promoted the progression of PTC by regulating the miR-7/EGFR axis. ciRS-7 is a promising prognostic biomarker and therapeutic target in PTC.

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High expression and localization of β-catenin and epidermal growth factor receptor identify high risk papillary thyroid carcinoma patients

Experimental and Molecular Pathology ◽

10.1016/j.yexmp.2018.08.001 ◽

2018 ◽

Vol 105 (2) ◽

pp. 181-189 ◽

Cited By ~ 2

Author(s):

Tijana Išić Denčić ◽

Aleksandar Bartolome ◽

Sonja Šelemetjev ◽

Ilona Đorić ◽

Svetislav Tatić ◽

...

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

High Risk ◽

Papillary Thyroid Carcinoma ◽

Epidermal Growth Factor ◽

Thyroid Carcinoma ◽

Growth Factor Receptor ◽

High Expression ◽

Papillary Thyroid ◽

Epidermal Growth

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Epidermal growth factor receptor gene mutations in papillary thyroid carcinoma

International Journal of Cancer ◽

10.1002/ijc.24250 ◽

2008 ◽

Vol 124 (11) ◽

pp. 2744-2749 ◽

Cited By ~ 34

Author(s):

Katsuhiro Masago ◽

Ryo Asato ◽

Shiro Fujita ◽

Shigeru Hirano ◽

Yoshihiro Tamura ◽

...

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Papillary Thyroid Carcinoma ◽

Epidermal Growth Factor ◽

Thyroid Carcinoma ◽

Receptor Gene ◽

Growth Factor Receptor ◽

Gene Mutations ◽

Papillary Thyroid ◽

Epidermal Growth

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Increased Eps15 homology domain 1 and RAB11FIP3 expression regulate breast cancer progression via promoting epithelial growth factor receptor recycling

Tumor Biology ◽

10.1177/1010428317691010 ◽

2017 ◽

Vol 39 (2) ◽

pp. 101042831769101 ◽

Cited By ~ 10

Author(s):

Dandan Tong ◽

Ya-Nan Liang ◽

AA Stepanova ◽

Yu Liu ◽

Xiaobo Li ◽

...

Keyword(s):

Breast Cancer ◽

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Growth Factor Receptor ◽

Epithelial Growth Factor Receptor ◽

Epithelial Growth Factor ◽

Epidermal Growth ◽

Epithelial Growth ◽

Eps15 Homology Domain

Recent research indicates that the C-terminal Eps15 homology domain 1 is associated with epithelial growth factor receptor–mediated endocytosis recycling in non-small-cell lung cancer. The aim of this study was to determine the clinical significance of Eps15 homology domain 1 gene expression in relation to phosphorylation of epithelial growth factor receptor expression in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Eps15 homology domain 1, RAB11FIP3, and phosphorylation of epithelial growth factor receptor expression via immunohistochemistry. The clinical significance was assessed via a multivariate Cox regression analysis, Kaplan–Meier curves, and the log-rank test. Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor were upregulated in 60.46% (185/306) and 53.92% (165/306) of tumor tissues, respectively, as assessed by immunohistochemistry. The statistical correlation analysis indicated that Eps15 homology domain 1 overexpression was positively correlated with the increases in phosphorylation of epithelial growth factor receptor ( r = 0.242, p < 0.001) and RAB11FIP3 ( r = 0.165, p = 0.005) expression. The multivariate Cox proportional hazard model analysis demonstrated that the expression of Eps15 homology domain 1 alone is a significant prognostic marker of breast cancer for the overall survival in the total, chemotherapy, and human epidermal growth factor receptor 2 (−) groups. However, the use of combined expression of Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor markers is more effective for the disease-free survival in the overall population, chemotherapy, and human epidermal growth factor receptor 2 (−) groups. Moreover, the combined markers are also significant prognostic markers of breast cancer in the human epidermal growth factor receptor 2 (+), estrogen receptor (+), and estrogen receptor (−) groups. Eps15 homology domain 1 has a tumor suppressor function, and the combined marker of Eps15 homology domain 1/phosphorylation of epithelial growth factor receptor expression was identified as a better prognostic marker in breast cancer diagnosis. Furthermore, RAB11FIP3 combines with Eps15 homology domain 1 to promote the endocytosis recycling of phosphorylation of epithelial growth factor receptor.

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Antivascular Therapy of Human Follicular Thyroid Cancer Experimental Bone Metastasis by Blockade of Epidermal Growth Factor Receptor and Vascular Growth Factor Receptor Phosphorylation

Cancer Research ◽

10.1158/0008-5472.can-04-4196 ◽

2005 ◽

Vol 65 (11) ◽

pp. 4716-4727 ◽

Cited By ~ 41

Author(s):

Maher Nabil Younes ◽

Orhan Gazi Yigitbasi ◽

Young Wook Park ◽

Sun-Jin Kim ◽

Samar A. Jasser ◽

...

Keyword(s):

Epidermal Growth Factor Receptor ◽

Thyroid Cancer ◽

Growth Factor ◽

Bone Metastasis ◽

Epidermal Growth Factor ◽

Growth Factor Receptor ◽

Follicular Thyroid Cancer ◽

Vascular Growth ◽

Vascular Growth Factor ◽

Epidermal Growth

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CLM3, a Multitarget Tyrosine Kinase Inhibitor With Antiangiogenic Properties, Is Active Against Primary Anaplastic Thyroid Cancer In Vitro and In Vivo

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2013-2321 ◽

2014 ◽

Vol 99 (4) ◽

pp. E572-E581 ◽

Cited By ~ 24

Author(s):

Alessandro Antonelli ◽

Guido Bocci ◽

Poupak Fallahi ◽

Concettina La Motta ◽

Silvia Martina Ferrari ◽

...

Keyword(s):

Epidermal Growth Factor Receptor ◽

Thyroid Cancer ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Tyrosine Kinase ◽

Cell Line ◽

Growth Factor Receptor ◽

Anaplastic Thyroid Cancer ◽

Antiangiogenic Activity ◽

Epidermal Growth

Context and Objective: We have studied the antitumor activity of a pyrazolo[3,4-d]pyrimidine compound (CLM3) proposed for a multiple signal transduction inhibition [including the RET tyrosine kinase, epidermal growth factor receptor, and vascular endothelial growth factor (VEGF) receptor and with antiangiogenic activity] in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C (undifferentiated thyroid cancer), and in an ATC-cell line (AF). Design and Main Outcome Measures: CLM3 was tested in primary ATC cells at the concentrations of 5, 10, 30, and 50 μM; in 8305C cells, in AF cells, at 1, 5, 10, 30, 50, or 100 μM; and in AF cells in CD nu/nu mice. Results: CLM3 significantly inhibited the proliferation of 8305C and AF cells, also inducing apoptosis. A significant reduction of proliferation with CLM3 in ATC cells (P < .01, ANOVA) was shown. CLM3 increased the percentage of apoptotic ATC cells dose dependently (P < .001, ANOVA) and inhibited migration (P < .01) and invasion (P < .001). The AF cell line was injected sc in CD nu/nu mice, and tumor masses became detectable 15 days later. CLM3 (50 mg/kg per die) significantly inhibited tumor growth (starting 16 d after the beginning of treatment). CLM3 significantly decreased the VEGF-A expression and microvessel density in AF tumor tissues. Furthermore, CLM3 inhibited epidermal growth factor receptor, AKT, and ERK1/2 phosphorylation and down-regulated cyclin D1 in 8305C and AF cells. Conclusions: The antitumor and antiangiogenic activity of a pyrazolo[3,4-d]pyrimidine compound (CLM3) is very promising in anaplastic thyroid cancer, opening the way to a future clinical evaluation.

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