IGFBP7 inhibits cell proliferation by suppressing AKT activity and cell cycle progression in thyroid carcinoma

Zhang, Le; Lian, Rong; Zhao, Jingjing; Feng, Xianming; Ye, Runyi; Pan, Langxing; Wu, Jueheng; Li, Mengfeng; Huan, Yongbo; Cai, Junchao

doi:10.1186/s13578-019-0310-2

Cited by 28 publications

(32 citation statements)

References 48 publications

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“…37 Low levels of phosphorylated AKT upregulated p21 cip1 and p27 kip1 leading to the induction of G1/ S-phase arrest in thyroid carcinoma cells. 38 Furthermore, downregulation of phosphorylated AKT inhibited proliferation and induced G1/S-phase arrest and apoptosis in glioma cells resulting to a significant reduction in the levels of Bcl-2 and cyclin D1. 39 In the present study, GA attenuated phosphorylation of PI3K and AKT, which was probably responsible for cell cycle arrest and apoptosis in GC cells.…”

Section: Discussionmentioning

confidence: 99%

<p>Glycyrrhizic Acid Inhibits Proliferation of Gastric Cancer Cells by Inducing Cell Cycle Arrest and Apoptosis</p>

Wang¹,

Ge²,

Qu³

et al. 2020

CMAR

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Glycyrrhizic acid (GA) is the main active ingredient extracted from Chinese herb licorice root, and it shows anti-tumor effects in many cancer types, while its role in gastric cancer (GC) is still unknown. In this study, we evaluated the effects of GA on GC cells and explored the underlying mechanisms. Methods: The anti-proliferation effect of GA on GC cells was assessed by CCK-8, colony formation, and EdU assay. The effects of GA on cell cycle and apoptosis were detected by flow cytometer. Western blotting was performed to explore the underlying mechanisms. Results: Our results showed that GA had a time-and dose-dependent inhibitory effect on proliferation of GC cells. Flow cytometer analysis demonstrated that GA would lead to G1/ S-phase arrest and apoptosis. GA treatment down-regulated the levels of G1 phase-related proteins, including cyclin D1, D2, D3, E1, and E2. In terms of apoptosis, GA treatment upregulated the levels of Bax, cleaved PARP, and pro-caspase-3,-8,-9, but did not influence their cleavage patterns. The expression of Bcl-2, survivin and p65 was attenuated after treatment. Besides, GA would down-regulate the phosphorylation of PI3K/AKT pathway. Conclusion: This study focused on inhibitory effect of GA on GC cells by inducing cell cycle arrest and apoptosis. Several important cyclins-and apoptosis-related proteins were involved in the regulation of GA to GC cells, and phosphorylated PI3K and AKT were attenuated. The results of this study indicated that GA is a potential and promising anticancer drug for GC.

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Section: Discussionmentioning

confidence: 99%

<p>Glycyrrhizic Acid Inhibits Proliferation of Gastric Cancer Cells by Inducing Cell Cycle Arrest and Apoptosis</p>

Wang¹,

Ge²,

Qu³

et al. 2020

CMAR

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“…PTC accounted for 80% of TCs, and showed a better prognosis. However, patients with PDTC or ATC due to rapid progression and local or distant metastasis frequently led to worse prognosis [1][2][3][4]. In addition to the characteristics of rapid growth of tumor cells, metastasis has been one of the hallmarks in cancer, leading to tumor dissemination and aggressiveness [26].…”

Section: Discussionmentioning

confidence: 99%

“…Based on the degree of differentiation, TC is categorized into three kinds, which include well-differentiated thyroid carcinomas such as papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC), as well as poorly-differentiated thyroid carcinoma (PDTC) and anaplastic thyroid cancer (ATC). Of these, PDTC and ATC accounted for only 15% and less than 5% of all TC cases [2]. These types of thyroid carcinomas are responsible for more than half of all TC mortalities that occur due to early lymph node (LN) metastasis and invasion of neighboring organs [3].…”

Section: Introductionmentioning

confidence: 99%

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

Zhao

Kang

et al. 2020

Cell Biosci

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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.

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“…As an important protein coding gene, studies of IGFBP7 have mainly focused on its suppressive role in various human malignancies, including thyroid carcinoma, cholangiocarcinoma, gastric cancer, hepatocellular carcinoma and breast cancer. 11,13,14 However, there are reports that the effects of IGFBP7 involve insulin resistance and the risk of metabolic syndrome, 33 which are considered closely related to the development of osteoporosis. [34][35][36] More importantly, recent studies have reported that IGFBP7 may play considerable roles in bone metabolism.…”

Section: Discussionmentioning

confidence: 99%

IGFBP7 acts as a negative regulator of RANKL‐induced osteoclastogenesis and oestrogen deficiency‐induced bone loss

Hou

Chen

et al. 2019

Cell Proliferation

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Objectives Insulin‐like growth factor‐binding protein 7 (IGFBP7) is a low‐affinity insulin growth factor (IGF) binder that may play an important role in bone metabolism. We previously reported that IGFBP7 enhanced osteogenic differentiation of bone marrow‐derived mesenchymal stem cells (BMSCs) via the Wnt/β‐catenin signalling pathway. In this study, we tried to reveal its function in osteoclast differentiation and osteoporosis. Methods We used both in vitro and in vivo studies to investigate the effects of IGFBP7 on RANKL‐induced osteoclastogenesis and osteoporosis, together with the underlying molecular mechanisms of these processes. Results We show that IGFBP7 inhibited receptor activation of nuclear factor‐κB (NF‐κB) ligand (RANKL)‐induced osteoclastogenesis, F‐actin ring formation and bone resorption, which was confirmed by using recombinant IGFBP7 protein, lentivirus and siRNA. The NF‐κB signalling pathway was inhibited during this process. Moreover, in a mouse ovariectomy‐induced osteoporosis model, IGFBP7 treatment attenuated osteoporotic bone loss by inhibiting osteoclast activity. Conclusions Taken together, these findings show that IGFBP7 suppressed osteoclastogenesis in vitro and in vivo and suggest that IGFBP7 is a negative regulator of osteoclastogenesis and plays a protective role in osteoporosis. These novel insights into IGFBP7 may facilitate the development of potential treatment strategies for oestrogen deficiency‐induced osteoporosis and other osteoclast‐related disorders.

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IGFBP7 inhibits cell proliferation by suppressing AKT activity and cell cycle progression in thyroid carcinoma

Cited by 28 publications

References 48 publications

<p>Glycyrrhizic Acid Inhibits Proliferation of Gastric Cancer Cells by Inducing Cell Cycle Arrest and Apoptosis</p>

<p>Glycyrrhizic Acid Inhibits Proliferation of Gastric Cancer Cells by Inducing Cell Cycle Arrest and Apoptosis</p>

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

IGFBP7 acts as a negative regulator of RANKL‐induced osteoclastogenesis and oestrogen deficiency‐induced bone loss

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