title: Overexpression of DIXDC1 correlates with enhanced cell growth and poor prognosis in human pancreatic ductal adenocarcinoma.
abstract: Disheveled-axin (DIX) domain containing 1 (DIXDC1), a protein containing a coiled-coil domain and a DIX domain, is involved in the progression of multiple cancers. However, the role of DIXDC1 in human pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this study, we investigated the role and prognostic value of DIXDC1 in the development of human PDAC. Western blot analysis revealed that DIXDC1 was highly expressed in PDAC tissues and cell lines. Immunohistochemistry on 165 paraffin-embedded sections showed that high expression of DIXDC1 was significantly correlated with tumor size (P = .002), histological differentiation (P = .001), tumor node metastasis (TNM) stage (P = .001), and the proliferation marker Ki-67 (P = .000). Importantly, Kaplan-Meier analysis revealed that high expression of DIXDC1 was obviously correlated with worsened overall survival (P < .001). In vitro, using serum starvation-refeeding experiments, our results suggested that DIXDC1 was up-regulated in proliferating PDAC cells, together with the percentage of cells at the S phase, and was correlated with the expression of cyclin D1. In addition, depletion of DIXDC1 decreased PCNA and cyclin D1 levels. Accordingly, CCK-8, colony formation, and flow cytometry analyses revealed that knocking down DIXDC1 induced growth impairment and G1/S cell cycle arrest in PDAC cells, while overexpression of DIXDC1 led to accelerated cell proliferation and cell cycle progression. On the basis of these results, we propose that DIXDC1 could play an important role in the tumorigenesis of PDAC and serve as a potential therapeutical target to prevent PDAC progression.
authors: Department of General Surgey, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors: Xiaohong
authors: X
authors: Li
authors: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu, China.
authors: Ying
authors: Y
authors: Xiao
authors: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors: Shaoqing
authors: S
authors: Fan
authors: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors: Mingbing
authors: M
authors: Xiao
authors: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors: Xiaotong
authors: X
authors: Wang
authors: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu, China.
authors: Xiaolin
authors: X
authors: Zhu
authors: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors: Xudong
authors: X
authors: Chen
authors: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors: Chunsun
authors: C
authors: Li
authors: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors: Guijuan
authors: G
authors: Zong
authors: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China. Electronic address: zhougx@ntu.edu.cn.
authors: Guoxiong
authors: G
authors: Zhou
authors: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu, China; Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, 226001, Jiangsu, China. Electronic address: Chwan@ntu.edu.cn.
authors: Chunhua
authors: C
authors: Wan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D015854:Up-Regulation
chemical_list: C530104:CCND1 protein, human; C513335:DIXDC1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D018809:Proliferating Cell Nuclear Antigen; D019938:Cyclin D1
keywords: Cell cycle progression; Cell proliferation; DIXDC1; Pancreatic ductal adenocarcinoma; Prognosis