Identification of AK4 as a novel therapeutic target for serous ovarian cancer

Abstract

The present study aimed to assess the expression level of adenylate kinase 4 (AK4) in human serous ovarian cancer (SOC) tissues and investigate the possible involvement of AK4 in SOC progression. Bioinformatics analysis based on The Cancer Genome Atlas (TCGA) database and immunohistochemical (IHC) assays were performed to assess the expression level of AK4 in human SOC tissues. Clinical pathological features of patients with SOC were also evaluated. Colony formation, MTT, wound healing and Transwell assays were conducted to investigate the effects of AK4 on the proliferation, migration, and invasion of SOC cells in vitro . Mouse xenograft and lung metastasis models were developed to evaluate the effects of AK4 on tumor growth and metastasis in vivo . High expression levels of AK4 were identified in human SOC tissues compared with in normal tissues according to TCGA database and the results of IHC assays. A contribution of AK4 to tumor growth and metastasis of SOC cells in vivo was also shown. The present study confirmed the involvement of AK4 in the progression of SOC, and the results indicated that AK4 could serve as a novel therapeutic target for SOC treatment.

Adenylate Kinase 4—A Key Regulator of Proliferation and Metabolic Shift in Human Pulmonary Arterial Smooth Muscle Cells via Akt and HIF-1α Signaling Pathways

“…This indicates that AK4 plays an essential role in PASMCs not only by regulating cellular responses to hypoxia but also under physiological conditions. Similar effects of AK4 targeting have been described for immortalized human embryonic kidney cells [ 33 ] and some cancer cell lines [ 28 , 29 , 37 ]. This points to a common fundamental role of AK4 in cancer cells and PASMCs.…”

“…In humans, nine adenylate kinase isoenzymes (AK1–AK9) are known, displaying different organ and subcellular distributions, kinetic properties, and functions in response to diverse physiological and pathological stimuli [ 19 , 20 , 21 ]. A rapidly growing body of research unveils the importance of AK isoenzymes in the regulation of numerous cellular processes, including cell differentiation and proliferation, motility, metabolic reprogramming, and cancer progression [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ].…”

Disrupting the CmP signaling network unveils novel biomarkers for triple negative breast cancer in Caucasian American women

“…During our studies, we found an overwhelming amount of literature support, demonstrating that the majority of our identified biomarkers had confirmed roles in signaling pathways confirmed in cancer progression, validating their potential as prognosis biomarkers in CAW-TNBCs. AK4, observed to be down-regulated in our studies, is involved in the progression of Serous ovarian cancer [81], and AK4 depletion was shown to impair cell proliferation and invasion in MCF7 as well as MB231 breast cancer cells [82]. CAV1, a tumor suppressor gene candidate, is a negative regulator of the Ras-p42/44 mitogen-activated kinase cascade [83], and has been shown to play a critical role in the progression of breast cancer through autophagy, invasion, proliferation, apoptosis, migration, and breast cancer metastasis [84].…”

Targeted Quantitative Profiling of GTP-Binding Proteins Associated with Metastasis of Melanoma Cells

“…There is considerable research showing that AK4 is a prognostic marker in several types of cancer, including ovarian cancer and bladder cancer, where an increased expression of AK4 is usually associated with poorer patient survival. In lung cancer, elevated AK4 expression could promote metastasis by downregulating the transcription factor ATF3, which leads to MMP2 induction .…”