AK4 Promotes the Progression of HER2-Positive Breast Cancer by Facilitating Cell Proliferation and Invasion

• Published in: Disease markers Vol. 2019; no. 2019; pp. 1 - 9
• Main Authors: Li, Zhi-Xi, Jiang, Wen-Jun, Qiu, Rong-Lin, Wu, Chi-Hua, Yin, Yan-Tao, Zhang, Jie, Deng, Xiao-Geng
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 2019; Hindawi; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Adenylate kinase; Adenylate Kinase - metabolism; Animals; Apoptosis; Biomarkers, Tumor - metabolism; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cancer therapies; Cell culture; Cell growth; Cell Proliferation; Chemotherapy; Combined Modality Therapy; Depletion; Energy metabolism; Epidermal growth factor; ErbB-2 protein; Female; Growth factors; Homeostasis; Hospitals; Humans; Kinases; Lung cancer; Lung Neoplasms - metabolism; Lung Neoplasms - secondary; Lung Neoplasms - therapy; Lymph nodes; Lymphatic Metastasis; Mammary gland; Mammary glands; Medical prognosis; Medical research; Metabolism; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Mitochondria; Neoplasm Invasiveness; Patients; Plasmids; Prognosis; Receptor, ErbB-2 - metabolism; Survival Rate; Therapeutic applications; Tissues; Transcription factors; Tumor Cells, Cultured; Tumorigenesis; Tumors; Xenograft Model Antitumor Assays; China; United Kingdom > UK
• ISSN: 0278-0240; 1875-8630
• DOI: 10.1155/2019/8186091

Breast cancer (BC) is a type of malignant tumor originating from the epithelial tissue of the mammary gland, and about 20% of breast cancers are human epidermal growth factor receptor 2 positive (HER2+), which is a subtype with more aggression. Recently, HER2-positive breast cancer is often accompanied by poor prognosis of patients, and targeted therapy showed a promising prospect. To combat this disease, novel therapeutic targets are still needed. Adenylate kinase 4 (AK4) is a member of the adenylate kinase family and is expressed in the mitochondrial matrix. AK4 is involved in multiple cellular functions such as energy metabolism homeostasis. Interestingly, AK4 was observed highly expressed in several tumor tissues, and the involvement of AK4 in cancer development was generally revealed. However, the possible role of AK4 on the growth and development of breast cancer is still unclear. Here, we investigated the possible functions of AK4 on the progression of HER2-positive breast cancer. We found the high expression of AK4 in HER2-positive breast cancer tissues from patients who received surgical treatment. Additionally, AK4 expression levels were obviously correlated with clinical-pathological features, including pTNM stage (P=0.017) and lymph node metastasis (P=0.046). We mechanically confirmed that AK4 depletion showed the obvious impairment of cell proliferation and invasion in MCF7 and MDA-MB-231 cells. AK4 also facilitates tumor growth and metastasis of HER2-positive breast cancer in vivo. In conclusion, we identified and mechanically confirmed that AK4 is a novel therapeutic target of HER2-positive breast cancer.