Retraction Note to: The Akt inhibitor KP372-1 suppresses Akt activity and cell proliferation and induces apoptosis in thyroid cancer cells

Context: ZIC1 has been reported to be overexpressed and plays an oncogenic role in some brain tumors, whereas it is inactivated by promoter hypermethylation and acts as a tumor suppressor in gastric and colorectal cancers. However, until now, its biological role in thyroid cancer remains totally unknown. Objectives: The aim of this study is to explore the biological functions and related molecular mechanism of ZIC1 in thyroid carcinogenesis. Setting and Design: Quantitative RT-PCR (qRT-PCR) was performed to evaluate mRNA expression of investigated genes. Methylation-specific PCR was used to analyze promoter methylation of the ZIC1 gene. The functions of ectopic ZIC1 expression in thyroid cancer cells were determined by cell proliferation and colony formation, cell cycle and apoptosis, as well as cell migration and invasion assays. Results: ZIC1 was frequently down-regulated by promoter hypermethylation in both primary thyroid cancer tissues and thyroid cancer cell lines. Moreover, our data showed that ZIC1 hypermethylation was significantly associated with lymph node metastasis in patients with papillary thyroid cancer. Notably, restoration of ZIC1 expression in thyroid cancer cells dramatically inhibited cell proliferation, colony formation, migration and invasion, and induced cell cycle arrest and apoptosis by blocking the activities of the phosphatidylinositol-3-kinase (PI3K)/Akt and RAS/RAF/MEK/ERK (MAPK) pathways, and enhancing FOXO3a transcriptional activity. Conclusions: Our data demonstrate that ZIC1 is frequently inactivated by promoter hypermethyaltion and functions as a tumor suppressor in thyroid cancer through modulating PI3K/Akt and MAPK signaling pathways and transcription factor FOXO3a.

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Protein Kinase A-Independent Inhibition of Proliferation and Induction of Apoptosis in Human Thyroid Cancer Cells by 8-Cl-Adenosine

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-2331 ◽

2008 ◽

Vol 93 (3) ◽

pp. 1020-1029 ◽

Cited By ~ 15

Author(s):

Audrey J. Robinson-White ◽

Hui-Pin Hsiao ◽

Wolfgang W. Leitner ◽

Elizabeth Greene ◽

Andrew Bauer ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Thyroid Cancer ◽

Protein Kinase ◽

Protein Kinase A ◽

Cancer Cells ◽

Human Thyroid ◽

Inhibition Of Proliferation ◽

Thyroid Cancer Cells ◽

Kinase A

Abstract Purpose: Protein kinase A (PKA) affects cell proliferation in many cell types and is a potential target for cancer treatment. PKA activity is stimulated by cAMP and cAMP analogs. One such substance, 8-Cl-cAMP, and its metabolite 8-Cl-adenosine (8-Cl-ADO) are known inhibitors of cancer cell proliferation; however, their mechanism of action is controversial. We have investigated the antiproliferative effects of 8-Cl-cAMP and 8-CL-ADO on human thyroid cancer cells and determined PKA’s involvement. Experimental Design: We employed proliferation and apoptosis assays and PKA activity and cell cycle analysis to understand the effect of 8-Cl-ADO and 8-Cl-cAMP on human thyroid cancer and HeLa cell lines. Results: 8-Cl-ADO inhibited proliferation of all cells, an effect that lasted for at least 4 d. Proliferation was also inhibited by 8-Cl-cAMP, but this inhibition was reduced by 3-isobutyl-1-methylxanthine; both drugs stimulated apoptosis, and 3-isobutyl-1-methylxanthine drastically reduced 8-Cl-cAMP-induced cell death. 8-Cl-ADO induced cell accumulation in G1/S or G2/M cell cycle phases and differentially altered PKA activity and subunit levels. PKA stimulation or inhibition and adenosine receptor agonists or antagonists did not significantly affect proliferation. Conclusions: 8-Cl-ADO and 8-Cl-cAMP inhibit proliferation, induce cell cycle phase accumulation, and stimulate apoptosis in thyroid cancer cells. The effect of 8-Cl-cAMP is likely due to its metabolite 8-Cl-ADO, and PKA does not appear to have direct involvement in the inhibition of proliferation by 8-Cl-ADO. 8-Cl-ADO may be a useful therapeutic agent to be explored in aggressive thyroid cancer.

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miR-9-5p Increases Sensitivity to Cisplatin in Thyroid Cancer Cells by Down-Regulating BRAF Expression

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2019.2054 ◽

2019 ◽

Vol 9 (6) ◽

pp. 751-759

Author(s):

Wanzhi Chen ◽

Jichun Yu ◽

Rong Xie ◽

Meijun Zhong

Keyword(s):

Cell Proliferation ◽

Wound Healing ◽

Thyroid Cancer ◽

Cancer Cells ◽

Cell Apoptosis ◽

Cell Number ◽

Luciferase Reporter ◽

Reporter Assay ◽

Thyroid Cancer Cells ◽

Dual Luciferase Reporter Assay

Objective: To explore the expression of miR-9-5p and BRAF in cisplatin resistant strain thyroid cancer cells and reversal effect of drug resistance as well as the possible mechanism. Methods: The cisplatin-resistant thyroid cancer cells (FTC-133/DDP and TPC-1/DDP) were respectively divided into 3 groups as NC, DDP and DDP + miRNA groups. Measuring cell proliferation by MTT assay and cell apoptosis by flow cytometry; Evaluating invasion cell number and wound healing rates by transwell and wound healing assay. The relative proteins (BRAF, Mek and Erk1/2) were measured by WB assay. The correlation between miR-9-5p and BRAF by dual-luciferase reporter assay in FTC-133/DDP and TPC-1/DDP cells. Results: In FTC-133/DDP and TPC-1/DDP cells experiment, compared with DDP group, with miR-9-5p supplement, the cell proliferation rats were significantly depressed with cell apoptosis increasing (P < 0.001, respectively); invasion cell number and wound healing rats were significantly down-regulation (P < 0.001, respectively) in DDP + miRNA groups. Meanwhile, the BRAF, Mek and Erk1/2 proteins expressions were significantly depressed in DDP + miRNA groups were significantly suppressed compared with those in DDP groups (P < 0.001, respectively). By dual-luciferase reporter assay, BRAF was the target gene of miR-9-5p in FTC133/DDP and TPC-1/DDP cells. Conclusion: miR-9-5p increases sensitivity to cisplatin in thyroid cancer cells by down-regulating BRAF expression.

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PTEN deficiency and mutant p53 confer glucose-addiction to thyroid cancer cells: impact of glucose depletion on cell proliferation, cell survival, autophagy and cell migration

Genes & Cancer ◽

10.18632/genesandcancer.21 ◽

2014 ◽

Vol 5 (7-8) ◽

pp. 226-239 ◽

Cited By ~ 21

Author(s):

Federica Morani ◽

Suratchanee Phadngam ◽

Carlo Follo ◽

Rossella Titone ◽

Visa Thongrakard ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Migration ◽

Thyroid Cancer ◽

Cell Survival ◽

Cancer Cells ◽

Mutant P53 ◽

Glucose Depletion ◽

Thyroid Cancer Cells

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Sorafenib inhibits vascular endothelial cell proliferation stimulated by anaplastic thyroid cancer cells regardless of BRAF mutation status

International Journal of Oncology ◽

10.3892/ijo.2019.4881 ◽

2019 ◽

Cited By ~ 2

Author(s):

Sae Ishihara ◽

Naoyoshi Onoda ◽

Satoru Noda ◽

Yuka Asano ◽

Yukie Tauchi ◽

...

Keyword(s):

Cell Proliferation ◽

Thyroid Cancer ◽

Endothelial Cell ◽

Cancer Cells ◽

Vascular Endothelial Cell ◽

Anaplastic Thyroid Cancer ◽

Endothelial Cell Proliferation ◽

Vascular Endothelial ◽

Mutation Status ◽

Thyroid Cancer Cells

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The Akt-Specific Inhibitor MK2206 Selectively Inhibits Thyroid Cancer Cells Harboring Mutations That Can Activate the PI3K/Akt Pathway

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2010-2644 ◽

2011 ◽

Vol 96 (4) ◽

pp. E577-E585 ◽

Cited By ~ 65

Author(s):

Ruixin Liu ◽

Dingxie Liu ◽

Eliana Trink ◽

Ermal Bojdani ◽

Guang Ning ◽

...

Keyword(s):

Thyroid Cancer ◽

Cancer Cells ◽

Therapeutic Potential ◽

Mammalian Target Of Rapamycin ◽

Specific Inhibitor ◽

Akt Pathway ◽

Akt Inhibitor ◽

Cancer Cell Growth ◽

Ic50 Values ◽

Thyroid Cancer Cells

Abstract Context: The phosphoinositide 3-kinase (PI3K)/Akt pathway is widely postulated to be an effective therapeutic target in thyroid cancer. Objective: The aim of the study was to test the therapeutic potential of the novel Akt inhibitor MK2206 for thyroid cancer. Design: We examined the effects of MK2206 on thyroid cancer cells with respect to the genotypes of the PI3K/Akt pathway. Results: Proliferation of thyroid cancer cells OCUT1, K1, FTC133, C643, Hth7, and TPC1, which harbored PIK3CA, PTEN, Ras, or RET/PTC mutations that could activate the PI3K/Akt pathway, was potently inhibited by MK2206 with IC50 values mostly below or around 0.5 μm. In contrast, no potent inhibition by MK2206 was seen in most of the Hth74, KAT18, SW1736, WRO, and TAD2 cells that did not harbor mutations in the PI3K/Akt pathway. The inhibition efficacy was also genetic-selective. Specifically, the average inhibition efficacies were 59.2 ± 11.3 vs. 36.4 ± 8.8% (P = 0.005) at 1 μm MK2206 and 64.4 ± 11.5 vs. 38.5 ± 18.9% (P = 0.02) at 3 μm MK2206 for cells with mutations vs. cells without. The SW1736 cell, lacking mutations in the PI3K/Akt pathway, had minimal response to MK2206, but transfection with exogenous PIK3CA mutants, PIK3CA H1047R and E545K, significantly increased its sensitivity to MK2206. MK2206 also completely overcame the feedback activation of Akt from temsirolimus-induced mammalian target of rapamycin suppression, and the two inhibitors synergistically inhibited thyroid cancer cell growth. Conclusions: Our study demonstrates a genetic selectivity of MK2206 in inhibiting thyroid cancer cells by targeting the PI3K/Akt pathway, supporting a clinical trial in thyroid cancer.

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