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المؤلفون: Guiyuan Liu, Ning Xu, Haihua Zhou, Xiaolan You, Dehu Chen, Qinghong Liu, Xiaojun Zhao
المصدر: Cellular Physiology and Biochemistry, Vol 42, Iss 3, Pp 1025-1036 (2017)
مصطلحات موضوعية: 0301 basic medicine, Male, Pathology, Physiology, lcsh:Physiology, Metastasis, 0302 clinical medicine, lcsh:QD415-436, Neoplasm Metastasis, RNA, Small Interfering, Gene knockdown, Mice, Inbred BALB C, lcsh:QP1-981, biology, medicine.diagnostic_test, TOR Serine-Threonine Kinases, Stomach, Transfection, Middle Aged, Gene Expression Regulation, Neoplastic, ARK5, 030220 oncology & carcinogenesis, mTOR, Immunohistochemistry, Female, RNA Interference, Signal Transduction, medicine.medical_specialty, Epithelial-Mesenchymal Transition, Slug, Mice, Nude, lcsh:Biochemistry, 03 medical and health sciences, Western blot, Stomach Neoplasms, Cell Line, Tumor, medicine, Animals, Humans, Neoplasm Invasiveness, PI3K/AKT/mTOR pathway, Cancer, medicine.disease, biology.organism_classification, Repressor Proteins, 030104 developmental biology, Gastric Mucosa, Cancer research, Epithelial-mensenchymal transition, Gastric cancer, Protein Kinases
الوصف: Background/Aims: Gastric cancer (GC) is a common and lethal malignancy, and AMP-activated protein kinase-related kinase 5 (ARK5) has been discovered to promote cancer metastasis in certain types of cancer. In this study, we explored the role of ARK5 in GC invasion and metastasis. Methods: ARK5 and epithelial-mesenchymal transition (EMT)-related markers were determined by immunohistochemistry and western blot in GC specimens. Other methods including stably transfected against ARK5 into SGC7901 and AGS cells, western blot, migration and invasion assays in vitro and nude mice tumorigenicity in vivo were also employed. Results: The results demonstrated that ARK5 expression was increased and positively correlated with metastasis, EMT-related markers and poor prognosis in patients with GC. Knockdown of ARK5 expression remarkably suppressed GC cells invasion and metastasis via regulating EMT, rather than proliferation in vitro and in vivo . And knockdown of ARK5 expression in GC cells resulted in the down-regulation of the mTOR/p70S6k signals, Slug and SIP1. Conclusion: The elevated ARK5 expression was closely associated with cancer metastasis and patient survival, and it seemed to function in GC cells migration and invasion via EMT alteration, together with the alteration of the mTOR/p70S6k signals, Slug and SIP1, thus providing a potential therapeutic target for GC.
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