title: Kctd20 promotes the development of non-small cell lung cancer through activating Fak/AKT pathway and predicts poor overall survival of patients.
abstract: Kctd20 (potassium channel tetramerization protein domain containing 20) is a positive regulator of Akt signaling. However, the role of Kctd20 during the course of tumorigenesis and development is unclear. Using immunohistochemistry, we demonstrated that, in non-small cell lung cancer (NSCLC) patients, Kctd20 protein expression significantly correlates with advanced TNM stage (P < 0.001), positive status for regional lymph node metastasis (P = 0.019), and poor overall survival (P = 0.013). Proliferation and invasion assays showed that Kctd20 dramatically promotes the proliferation and invasion of NSCLC cells (P = 0.007 and P < 0.001, respectively). Subsequent Western Blot and qPCR experiments revealed an upregulation of Cyclin D1 and downregulation of E-cadherin in Kctd20-overexpressing cells. After depleting Kctd20, downregulaton of Cyclin D1, and upegulation of E-cadherin was observed. After overexpressing Kctd20, the levels of phosphorylated Fak (Tyr397) and Akt (Thr308) increased, while after transfection with Kctd20-siRNA these phosporylated proteins were downregulated. Moreover, in Kctd20-overexpressing cells, treatment with an Akt inhibitor reduced expression of p-Akt and Cyclin D1, enhanced E-cadherin expression, and did not impact p-Fak levels. When Kctd20-overexpressing cells were treated with a Fak inhibitor, the same effects were seen, and the level of p-Akt was reduced. Our results suggest that Kctd20 impacts proliferation and invasion of NSCLC through enhancing Fak (Tyr397) and Akt (Thr 308) phosphorylation. Kctd20 may predict prognosis and be targeted therapeutically in NSCLC.
authors.affiliation: Department of Pathology, College of Basic Medical Science and the First Hospital and of China Medical University, Shenyang, China.
authors.forename: Xiupeng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathology, College of Basic Medical Science and the First Hospital and of China Medical University, Shenyang, China.
authors.forename: Haijing
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Pathology, College of Basic Medical Science and the First Hospital and of China Medical University, Shenyang, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Pathology, College of Basic Medical Science and the First Hospital and of China Medical University, Shenyang, China.
authors.forename: Chuifeng
authors.initials: C
authors.lastname: Fan
authors.affiliation: Department of Pathology, College of Basic Medical Science and the First Hospital and of China Medical University, Shenyang, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, College of Basic Medical Science and the First Hospital and of China Medical University, Shenyang, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, College of Basic Medical Science and the First Hospital and of China Medical University, Shenyang, China.
authors.forename: Qingchang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Pathology, College of Basic Medical Science and the First Hospital and of China Medical University, Shenyang, China.
authors.forename: Yuan
authors.identifier: 0000-0001-7869-8099
authors.initials: Y
authors.lastname: Miao
mesh_terms: D015820:Cadherins / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015331:Cohort Studies; D019938:Cyclin D1 / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D016019:Survival Analysis; D014945:Wound Healing
chemical_list: C494432:BTBD10 protein, human; D015820:Cadherins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D019938:Cyclin D1; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; Fak; Kctd20; development; non-small cell lung cancer