Growth factor receptor bound protein-7 regulates proliferation, cell cycle, and mitochondrial apoptosis of thyroid cancer cells via MAPK/ERK signaling

• Published in: Molecular and cellular biochemistry 2020-09, Vol.472 (1-2), p.209-218
• Main Authors: Tang, Haili, Yang, Ping, Yang, Xiaojun, Peng, Shujia, Hu, Xi’e, Bao, Guoqiang
• Format: Article
• Language: English
• Subjects: Adenosine triphosphate; Apoptosis; ATP; BAX protein; Bcl-2 protein; Biochemistry; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Cancer; Cardiology; Case-Control Studies; Caspase-3; Cell Cycle; Cell Proliferation; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - genetics; Extracellular Signal-Regulated MAP Kinases - metabolism; Gene Expression Regulation, Neoplastic; Glucose metabolism; GRB7 Adaptor Protein - genetics; GRB7 Adaptor Protein - metabolism; Growth factors; Health aspects; Humans; Kinases; Lactose; Life Sciences; MAP kinase; Medical Biochemistry; Metabolic pathways; Mitochondria; Mitochondria - metabolism; Mitochondria - pathology; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - metabolism; Muscle proteins; Oncology; Pathogenesis; Polymerase chain reaction; Prognosis; Protein binding; Protein kinase; Protein kinases; Proteins; Receptors; Signaling; siRNA; Thyroid; Thyroid cancer; Thyroid gland; Thyroid Neoplasms - genetics; Thyroid Neoplasms - metabolism; Thyroid Neoplasms - pathology; Tumor Cells, Cultured; Tumors; Western blotting
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-020-03798-4

It is of great significance to explore the molecular mechanism of thyroid cancer (TC) pathogenesis for its improvement and therapy. Growth factor receptor bound protein-7 (GRB7) has been regarded as an important regulatory gene in the developments of various malignant tumors. Our study aimed to illustrate the role of GRB7 in the TC pathology mechanism. Firstly, GRB7 was found to be significantly upregulated in 49 cases of TC tissues and 5 TC cell lines by using real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. Silencing GRB7 with siRNA dramatically inhibited proliferation and induced cell cycle arrest in TC cells. Besides, GRB7 silence resulted in the decrease of adenosine triphosphate content, glucose uptake, and lactose production in TC cells and attenuated the activity and expression of mitochondrial respiratory complex. We also demonstrated that GRB7 downregulation increased the levels of Bax and caspase 3, and inhibited the expression of Bcl-2, suggesting the induced mitochondrial apoptosis. More importantly, our study proved that mitogen-activated protein kinase/extracellular-regulated protein kinases (MAPK/ERK) signaling played a crucial role in the regulation of GRB7 on TC cell functions. In general, the present research verified that GRB7 was upregulated during TC development and modulated the proliferation, cell cycle, and mitochondrial apoptosis of TC cells by activating MAPK/ERK pathway. This may provide a novel target for the therapeutic strategy of TC.