Ang1/Tie2 induces cell proliferation and migration in human papillary thyroid carcinoma via the PI3K/AKT pathway

Abstract

Abstract. The angiopoietin 1 (Ang1)/angiopoietin receptor (Tie2) signaling pathway may have a notable role in the pathogenesis of inflammatory diseases. The abnormal expression of angiopoietin 1 and Tie2 has also been reported in various malignant tumors, including papillary thyroid carcinoma (PTC). However, the role and mechanism of the Ang1/Tie2 pathway in the progression of PTC remains unclear. Therefore, the aims of the present study were to clarify this. Significantly high expression levels of Ang1 and Tie2 were observed in PTC tissues and cell lines. Furthermore, MTT and wound-healing assays revealed that the Ang1-mediated stimulation of human PTC cells resulted in increased proliferation and migration. Conversely, the downregulation of Tie2 levels using short hairpin RNA targeted at Tie2 abrogated the Ang1-mediated effect on cell proliferation and migration. In studying the expression of phosphoinositide-3 kinase (PI3K)/RAC serine/threonine-protein kinase (Akt) pathway, the upregulation of Ang1/Tie2 was found to be associated with the activation of the PI3K/Akt pathway in PTC. In conclusion, the data from the present study indicated that the Ang1/Tie2 induces PTC oncogenesis via the PI3K/Akt pathway, providing novel insights into human PTC therapy. IntroductionPapillary thyroid carcinoma (PTC) is the most prevalent histological thyroid carcinoma subtype, accounting for ~80% of cases (1,2). Although recent advances in diagnosis and treatment strategies have been made in clinical and experimental oncology, ≤30% of patients present with local/regional recurrence or distant metastasis within 10 years (2,3). Thus, the elucidation of the molecular mechanisms underlying PTC progression is urgently required in order to develop effective diagnostic, prognostic and therapeutic strategies.Receptor tyrosine kinases are cell surface proteins that transduce signals from extracellular growth factors intracellularly, to elicit biological responses (4). Receptor tyrosine kinases act as potent oncoproteins and are abnormally expressed in a number of cancer types, including gliomas (5). Angiopoietin-1 (Ang1) receptor (TEK, also known as Tie2) is a receptor tyrosine kinase that was identified as an endothelial-cell-specific receptor with a critical role in the modulation of vasculogenesis and remodeling (6). Tie2 expression occurs, and is partially maintained, during differentiation in human neural stem cells (7), but not in mature neurons (8). Dysregulated Tie2 expression has also been observed in several tumor tissues, including oral squamous cell carcinoma, breast, gastric, leukemia and thyroid cancer (9-13). These studies revealed that Tie2 expression is associated with the identification and prognosis of these cancer types (12). Ang1 is a secreted ligand for Tie2 that maintains vascular plasticity, perturbations in which can contribute to abnormal vascular growth (4). Daly et al (6) revealed that Ang2 functions as a Tie2 agonist in tumor models, limiting the effects of VEGF inhibition (6). Mitsutake et al (13) revealed ...

Angiopoietin1 Deficiency in Hepatocytes Affects the Growth of Colorectal Cancer Liver Metastases (CRCLM)

“…It is possible that tumor cells that metastasize into the liver stimulate Ang1 expression in their environment (hepatocytes), which is important for blood vessel formation and growth of the tumor. It has been recently reported in human papillary thyroid carcinoma that upregulation of Ang1-Tie2 signalling activates pathways that are involved in cancer cells survival, proliferation and metastasis [26]. Furthermore, in-vitro, knockdown of Ang1 expression decreased the proliferation and migration of breast cancer cells, and found that the Ang1 overexpression rescued proliferation and migration of these cancer cells [27].…”

Identification of Altered Circular RNA Expression in Serum Exosomes from Patients with Papillary Thyroid Carcinoma by High-Throughput Sequencing

“…In the present study, KEGG analysis showed that the DEGs were mainly concentrated in 16 signaling pathways, including the thyroid hormone signaling pathway, the PI3K-Akt signaling pathway, the AMPK signaling pathway, and the phosphatidylinositol signaling pathway. Both the PI3K-Akt signaling pathway and the AMPK signaling pathway have been shown to be involved in the development of thyroid carcinoma [35][36][37].…”

Sema4D/PlexinB1 promotes endothelial differentiation of dental pulp stem cells via activation of AKT and ERK1/2 signaling

“…32 Sema4D may upregulate HIF-1⍺ directly or via VEGF, which can enhance expression of HIF-1⍺. 48 Angiopoietin 1 (ANG1) plays a crucial role in the regulation of vasculogenesis and remodeling, 49 and promotes endothelial differentiation of embryonic stem cells (ESCs). 50 As ANG1 is upregulated by Sema4D stimulation, ANG1 probably also plays some role in promoting the endothelial differentiation of DPSCs.…”