scholarly journals GRP78 promotes metastasis by regulation of the endoplasmic reticulum stress through remodeling extracellular matrix in thyroid carcinoma

2020 ◽  
Author(s):  
Guohong Zhao ◽  
Jianqin Kang ◽  
Guanghui Xun ◽  
Jing Wei ◽  
Xiaoguang Wang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Er Stress ◽  
Anaplastic Thyroid Cancer ◽  
Proliferative Potential ◽  
Genomic Amplification ◽  
Ecm Remodeling ◽  
Kegg Pathways ◽  
Normal Tissues

Abstract Background Thyroid cancer(TC)is the most common type of endocrine malignant tumor and the incidence is increasing by years. Conventional surgery, radiotherapy and chemotherapy are difficult to improve significantly effects due to the aggression and metastasis of poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) which are the most malignant type of thyroid cancer. Glucose-regulated protein (GRP78) as the key molecule is related to tumor growth, apoptosis and metastasis. However, the mechanisms responsible for the effects of TC on GRP78 still need to be discussed. Therefore, the purpose of this study was to explore the presence of GRP78 and the potential mechanism of TC. Results GRP78 expression is increased in thyroid carcinoma tissues in comparison with the adjacent normal tissues. Besides, down-regulation of GRP78 significantly inhibited the metastatic and proliferative potential of ATC cells in vitro studies. In addition, tunicomycin (TM)-induced ER stress could up-regulate the expression of GRP78, PERK and XBP1 as well as reverse metastatic ability of GRP78 in TC cells. Bioinformatics and statistical analysis of gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for RNA-seq data from si-GRP78 and si-control showed GRP78 may regulate the ability of metastasis through the ECM remodeling in ATC cells, as well as the expression of ECM components such as COL1A1 and MMP13 were illustrated to be highly relevant to ATC. The analysis of GEPIA database confirmed that high genomic amplification of MMP13 and COL1A1 in TC tissues and were correlated with TNM stage. A further western blot analysis showed MMP13 may be the target of GRP78 in ATC cells and ER stress could activate the expression of MMP13 which was suppressed by depletion of GRP78. Conclusions GRP78 is an important regulator of metastasis under the ER stress. In addition, GRP78’s functions might be mediated by ECM remodeling in ATC cells, which implicates GRP78 as a therapeutic target in thyroid cancer.

scholarly journals Tunicamycin promotes metastasis through upregulating endoplasmic reticulum stress induced GRP78 expression in thyroid carcinoma

2020 ◽  
Author(s):  
Guohong Zhao ◽  
Jianqin Kang ◽  
Guanghui Xun ◽  
Jing Wei ◽  
Xiaoguang Wang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Er Stress ◽  
Anaplastic Thyroid Cancer ◽  
Sequencing Data ◽  
Genomic Amplification ◽  
Ecm Remodeling ◽  
Kegg Pathways ◽  
Normal Tissues ◽  
Underlying Mechanisms

Abstract Background: Thyroid cancer (TC) is the most common type of endocrine malignancy tumor and the incidence of it is increasing over years. Conventional surgery, radiotherapy and chemotherapy are difficult to improve the significant effects of it due to aggression and metastasis of poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC), which are regarded as the most malignant type of TC. Glucose-regulated protein (GRP78) is the key molecule of tumor growth, apoptosis and metastasis. However, the underlying mechanisms of GRP78 on TC still require discussion. This study aimed to explore the role of GRP78 and its potential mechanism in TC.Results: GRP78 expression was increased in TC tissues when compared with adjacent normal tissues. Besides, down-regulation of GRP78 significantly inhibited the metastatic and proliferative ability of ATC cells in in vitro studies. In addition, tunicamycin-induced ER stress up-regulated the expression of GRP78, PERK and XBP1 as well as reversed the metastatic ability of GRP78 in ATC cells. Bioinformatics and statistical analysis of gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for RNA-sequencing data from si-GRP78 and si-control showed that GRP78 might regulate the ability of metastasis through extracellular matrix (ECM) remodeling in ATC cells, as well as the expression of ECM components such as COL1A1 and MMP13 were shown to be highly relevant to ATC. The analysis of GEPIA database confirmed high genomic amplification of MMP13 and COL1A1 in TC tissues and showed correlation with TNM stage. Further western blotting analysis showed that MMP13 might be the target of GRP78 in ATC cells and ER stress could activate the expression of MMP13 that was suppressed by the GRP78 depletion.Conclusions: GRP78 acts as an important regulator of metastasis under ER stress. In addition, the function of GRP7 might be mediated by ECM remodeling in ATC cells, implicating it as a therapeutic target in TC.

scholarly journals Tunicamycin promotes metastasis through upregulating endoplasmic reticulum stress indu​ced GRP78 expression in thyroid carcinoma

2020 ◽  
Author(s):  
Guohong Zhao ◽  
Jianqin Kang ◽  
Guanghui Xun ◽  
Jing Wei ◽  
Xiaoguang Wang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Er Stress ◽  
Anaplastic Thyroid Cancer ◽  
Sequencing Data ◽  
Genomic Amplification ◽  
Ecm Remodeling ◽  
Kegg Pathways ◽  
Normal Tissues ◽  
Underlying Mechanisms

Abstract Background: Thyroid cancer (TC) is the most common type of endocrine malignancy and its incidence is increasing over years. Conventional surgery, radiotherapy and chemotherapy are difficult to improve the significant effects of it due to aggression and metastasis of poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC), and these are regarded as the most malignant types of TC. Glucose-regulated protein (GRP78) is the key molecule of tumor growth, apoptosis and metastasis. However, the underlying mechanisms of GRP78 in TC still require discussion. This study aimed to explore the role of GRP78 and its potential mechanism in TC.Results: GRP78 expression was increased in TC tissues when compared with adjacent normal tissues. Besides, down-regulation of GRP78 significantly inhibited the metastatic and proliferative ability of ATC cells in in vitro studies. In addition, tunicamycin-induced ER stress up-regulated the expression of GRP78, PERK and XBP1 as well as reversed the metastatic ability of GRP78 in ATC cells. Bioinformatics and statistical analysis of gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for RNA-sequencing data with regard to si-GRP78 and si-control showed that GRP78 might regulate the ability of metastasis through extracellular matrix (ECM) remodeling in ATC cells, as well as the expression of ECM components such as COL1A1 and MMP13, which were highly relevant to ATC cells. The analysis of GEPIA database confirmed that high genomic amplification of MMP13 and COL1A1 in TC tissues showed correlation with TNM stage. Further western blotting analysis showed that MMP13 might be the target of GRP78 in ATC cells and ER stress could activate the expression of MMP13 that is suppressed by GRP78 depletion.Conclusions: GRP78 acts as an important regulator of metastasis under ER stress. In addition, the function of GRP78 might be mediated by ECM remodeling in ATC cells, implicating it as a therapeutic target in TC.

scholarly journals Tunicamycin promotes metastasis through upregulating endoplasmic reticulum stress induced GRP78 expression in thyroid carcinoma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Guohong Zhao ◽  
Jianqin Kang ◽  
Guanghui Xu ◽  
Jing Wei ◽  
Xiaoguang Wang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Er Stress ◽  
Anaplastic Thyroid Cancer ◽  
Sequencing Data ◽  
Genomic Amplification ◽  
Ecm Remodeling ◽  
Kegg Pathways ◽  
Normal Tissues ◽  
Underlying Mechanisms

Abstract Background Thyroid cancer (TC) is the most common type of endocrine malignancy and its incidence is increasing over years. Conventional surgery, radiotherapy and chemotherapy are difficult to improve the significant effects of it due to aggression and metastasis of poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC), and these are regarded as the most malignant types of TC. Glucose-regulated protein (GRP78) is the key molecule of tumor growth, apoptosis and metastasis. However, the underlying mechanisms of GRP78 in TC still require discussion. This study aimed to explore the role of GRP78 and its potential mechanism in TC. Results GRP78 expression was increased in TC tissues when compared with adjacent normal tissues. Besides, down-regulation of GRP78 significantly inhibited the metastatic and proliferative ability of ATC cells in in vitro studies. In addition, tunicamycin-induced ER stress up-regulated the expression of GRP78, PERK and XBP1 as well as reversed the metastatic ability of GRP78 in ATC cells. Bioinformatics and statistical analysis of gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for RNA-sequencing data with regard to si-GRP78 and si-control showed that GRP78 might regulate the ability of metastasis through extracellular matrix (ECM) remodeling in ATC cells, as well as the expression of ECM components such as COL1A1 and MMP13, which were highly relevant to ATC cells. The analysis of GEPIA database confirmed that high genomic amplification of MMP13 and COL1A1 in TC tissues showed correlation with TNM stage. Further western blotting analysis showed that MMP13 might be the target of GRP78 in ATC cells and ER stress could activate the expression of MMP13 that is suppressed by GRP78 depletion. Conclusions GRP78 acts as an important regulator of metastasis under ER stress. In addition, the function of GRP78 might be mediated by ECM remodeling in ATC cells, implicating it as a therapeutic target in TC.

scholarly journals Characterization of LDD-2633 as a Novel RET Kinase Inhibitor with Anti-Tumor Effects in Thyroid Cancer

2021 ◽  
Vol 14 (1) ◽  
pp. 38
Author(s):  
Hyo Jeong Lee ◽  
Pyeonghwa Jeong ◽  
Yeongyu Moon ◽  
Jungil Choi ◽  
Jeong Doo Heo ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Kinase Inhibitor ◽  
Point Mutations ◽  
Carcinoma Cells ◽  
Medullary Thyroid ◽  
Potent Inhibition ◽  
Kinase Inhibitory Activity

Rearranged during transfection (RET), a receptor tyrosine kinase, is activated by glial cell line-derived neurotrophic factor family ligands. Chromosomal rearrangement or point mutations in RET are observed in patients with papillary thyroid and medullary thyroid carcinomas. Oncogenic alteration of RET results in constitutive activation of RET activity. Therefore, inhibiting RET activity has become a target in thyroid cancer therapy. Here, the anti-tumor activity of a novel RET inhibitor was characterized in medullary thyroid carcinoma cells. The indirubin derivative LDD-2633 was tested for RET kinase inhibitory activity. In vitro, LDD-2633 showed potent inhibition of RET kinase activity, with an IC50 of 4.42 nM. The growth of TT thyroid carcinoma cells harboring an RET mutation was suppressed by LDD-2633 treatment via the proliferation suppression and the induction of apoptosis. The effects of LDD-2633 on the RET signaling pathway were examined; LDD-2633 inhibited the phosphorylation of the RET protein and the downstream molecules Shc and ERK1/2. Oral administration of 20 or 40 mg/kg of LDD-2633 induced dose-dependent suppression of TT cell xenograft tumor growth. The in vivo and in vitro experimental results supported the potential use of LDD-2633 as an anticancer drug for thyroid cancers.

scholarly journals FK506-binding protein 5 promotes the progression of papillary thyroid carcinoma

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110083
Author(s):  
Zhenya Gao ◽  
Fang Yu ◽  
Huanxia Jia ◽  
Zhuo Ye ◽  
Shijie Yao
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Binding Protein ◽  
Progression Free Survival ◽  
Papillary Thyroid ◽  
Expression Levels ◽  
Fk506 Binding Protein ◽  
Normal Tissues ◽  
Induced Apoptosis

Objective To detect the expression of FK506-binding protein 5 (FKBP5) in human papillary thyroid carcinoma (PTC) tissues, and explore its possible role in the progression of PTC. Methods FKBP5 expression levels were assessed in 115 PTC tissues and corresponding normal tissues by immunohistochemistry. We also examined the correlations between FKBP5 expression and clinicopathological factors and survival in 75 patients with PTC. The effects of FKBP5 on the proliferation and apoptosis of PTC cells were detected by colony-formation, MTT, and flow cytometry assays, respectively. We further investigated the effects of FKBP5 on tumor growth in mice. Results We revealed high expression levels of FKBP5 in human PTC tissues compared with normal tissues. Furthermore, high FKBP5 expression was associated with an increased incidence of intraglandular dissemination, and lower overall and progression-free survival. FKBP5 depletion remarkably suppressed the proliferation and induced apoptosis of PTC cells in vitro. FKBP5 further contributed to the growth of PTC tumors in mice. Conclusions The results of this study demonstrated the potential involvement of FKBP5 in the progression of PTC, and confirmed FKBP5 as a novel therapeutic target for PTC treatment.

scholarly journals Metformin reduces glycometabolism of papillary thyroid carcinoma in vitro and in vivo

2017 ◽  
Vol 58 (1) ◽  
pp. 15-23 ◽  
Author(s):  
Chen-Tian Shen ◽  
Wei-Jun Wei ◽  
Zhong-Ling Qiu ◽  
Hong-Jun Song ◽  
Xin-Yun Zhang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Xenograft Model ◽  
Dependent Manner ◽  
Papillary Thyroid ◽  
Fdg Uptake ◽  
Dose Dependent

More aggressive thyroid cancer cells show a higher activity of glycometabolism. Targeting cancer cell metabolism has emerged as a novel approach to prevent or treat malignant tumors. Glucose metabolism regulation effect of metformin in papillary thyroid cancer was investigated in the current study. Human papillary thyroid carcinoma (PTC) cell lines BCPAP and KTC1 were used. Cell viability was detected by CCK8 assay. Glucose uptake and relative gene expression were measured in metformin (0–10 mM for 48 h)-treated cells by 18F-FDG uptake assay and western blotting analysis, respectively. MicroPET/CT imaging was performed to detect 18F-FDG uptake in vivo. After treatment with metformin at 0, 2.5, 5 and 10 mM for 48 h, the ratio of p-AMPK to total AMPK showed significant rising in a dose-dependent manner in both BCPAP and KTC1, whereas p-AKT and p-mTOR expression level were downregulated. 18F-FDG uptake reduced after metformin treatment in a dose-dependent manner, corresponding to the reduced expression level of HK2 and GLUT1 in vitro. Xenograft model of PTC using BCPAP cells was achieved successfully. MicroPET/CT imaging showed that in vivo 18F-FDG uptake decreased after treatment with metformin. Immunohistochemistry staining further confirmed the reduction of HK2 and GLUT1 expression in the tumor tissue of metformin-treated PTC xenograft model. In conclusion, metformin could reduce glucose metabolism of PTC in vitro and in vivo. Metformin, by targeting glycometabolism of cancer cells, could be a promising adjuvant therapy alternative in the treatment modality of advanced thyroid carcinoma.

Synergistic anticancer activity of sorafenib, paclitaxel, and radiation therapy on anaplastic thyroid cancer in vitro and in vivo

Head & Neck ◽  
2020 ◽  
Vol 42 (12) ◽  
pp. 3678-3684
Author(s):  
Soo Young Kim ◽  
Seok‐Mo Kim ◽  
Hojin Chang ◽  
Hang‐Seok Chang ◽  
Cheong Soo Park ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Thyroid Cancer ◽  
Anticancer Activity ◽  
Anaplastic Thyroid Cancer

scholarly journals Thyroid Carcinoma with Pituitary Metastases: 2 Case Reports and Literature Review

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Weiying Lim ◽  
Dawn Shaoting Lim ◽  
Chiaw Ling Chng ◽  
Adoree Yiying Lim
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Radioiodine Therapy ◽  
Follicular Thyroid Carcinoma ◽  
Case Reports ◽  
Anaplastic Thyroid Cancer ◽  
Anaplastic Thyroid Carcinoma ◽  
Pituitary Metastases ◽  
History Of ◽  
Loss Of Appetite

We present 2 patients with pituitary metastases from thyroid carcinoma—the first from anaplastic thyroid carcinoma and the second from follicular thyroid carcinoma. The first patient, a 50-year-old lady, presented with 2-week history of hoarseness of voice, dysphagia, dyspnoea, and neck swelling. Imaging revealed metastatic thyroid cancer to lymph nodes and bone. Histology from surgery confirmed anaplastic thyroid cancer. She was found to have pituitary metastases postoperatively when she presented with nonvertiginous dizziness. She subsequently underwent radiotherapy and radioiodine treatment but passed away from complications. The second patient, a 65-year-old lady, presented with loss of appetite and weight with increased goitre size and dyspnoea. Surgery was performed in view of compressive symptoms and histology confirmed follicular thyroid carcinoma. Imaging revealed metastases to bone, lung, and pituitary. She also had panhypopituitarism with hyperprolactinemia and diabetes insipidus. She received radioiodine therapy but eventually passed away from complications.

scholarly journals Antitumor Effect of Various Phytochemicals on Diverse Types of Thyroid Cancers

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 125 ◽  
Author(s):  
Hye-Ji Shin ◽  
Kyung-A Hwang ◽  
Kyung-Chul Choi
Keyword(s):  
Thyroid Cancer ◽  
Animal Studies ◽  
Anaplastic Thyroid Cancer ◽  
Thyroid Cancers ◽  
Anticancer Efficacy ◽  
Other Substances ◽  
English Articles ◽  
Thyroid Cancer Cells ◽  
Inhibit Cell Proliferation

Thyroid cancers developed from the tissues of the thyroid gland are classified into papillary (PTC), follicular (FTC), medullary (MTC), and anaplastic thyroid cancer (ATC). Although thyroid cancers have been generally known as mild forms of cancer, undifferentiated MTC and ATC have a more unfavorable prognosis than differentiated PTC and FTC because they are more aggressive and early metastatic. A variety of therapies such as surgery, radiotherapy, and chemotherapy have been currently used to treat thyroid cancer, but they still have limitations including drug resistance or unfavorable side effects. Phytochemicals are plant-derived chemicals having various physiological activities that are expected to be effective in cancer treatment. In this review, anticancer efficacy of phytochemicals, such as resveratrol, genistein, curcumin, and other substances in each type of thyroid cancer was introduced with their chemopreventive mechanisms. English articles related with thyroid cancer and anti-thyroid cancer of phytochemicals were searched from PubMed and Google Scholar. This article mainly focused on in vitro or animal studies on phytochemicals with anti-thyroid cancer activity. These various phytochemicals have been shown to induce apoptosis in all types of thyroid cancer cells, inhibit cell proliferation and invasion, and to be helpful in enhancing the effect of radioiodine therapy that is a typical therapy to thyroid cancer. These results suggest that thyroid cancer can be more effectively treated by the combinations of phytochemicals and the existing therapies or substances.

Abstract P120: Novel in vitro targeted combination therapies for anaplastic thyroid cancer

2021 ◽  
Author(s):  
Muthusamy Kunnimalaiyaan ◽  
Parag Parekh ◽  
Jalyn Golden ◽  
Ying Anderson ◽  
Stephen Lai ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Anaplastic Thyroid Cancer ◽  
Combination Therapies
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