title: VAV3 oncogene expression in colorectal cancer: clinical aspects and functional characterization.
abstract: Although colorectal cancer (CRC) is one of the most common malignancies worldwide, the current therapeutic approaches for advanced CRC are ineffective. In this study, we investigated the involvement of the VAV3 oncogene in tumor progression and in the prognosis of human CRC. The two patient cohorts in this study comprised 354 CRC cases from 1998 to 2005 with documented pathologic and clinical factors and clinical outcomes. VAV3 protein levels were significantly correlated with the depth of invasion (P = 0.0259), the nodal status (P < 0.0001), distant metastasis (P = 0.0354), the stage (P < 0.0001), and poor disease-free survival (P = 0.003). Multivariate Cox regression analysis showed that VAV3 overexpression is an independent prognostic marker for CRC (P = 0.041). In vitro experiments indicated that VAV3 knockdown inhibited CRC cell growth, spread, and xenograft proliferation. Mechanistic studies further revealed that VAV3 overexpression could dysregulate the expression of cell cycle control- and metastasis-related molecules by activating the PI3K-AKT signaling pathway in both CRC cells and xenografts. This study suggests that VAV3 overexpression could be a useful marker for predicting the outcomes of CRC patients and that VAV3 targeting represents a potential modality for treating CRC.
authors: 1] Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan [2] The Superintendent's Office, Chi Mei Hospital Chiali, Tainan, Taiwan.
authors: Yih-Huei
authors: YH
authors: Uen
authors: 1] Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan [2] Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors: Chia-Lang
authors: CL
authors: Fang
authors: 1] Department of Cosmeceutics, China Medical University, Taichung, Taiwan [2] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Texas, USA [3] Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
authors: You-Cheng
authors: YC
authors: Hseu
authors: Institute of Nutrition, China Medical University, Taichung, Taiwan.
authors: Pei-Chun
authors: PC
authors: Shen
authors: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Texas, USA [2] Institute of Nutrition, China Medical University, Taichung, Taiwan.
authors: Hsin-Ling
authors: HL
authors: Yang
authors: Department of Pharmacy, Chi Mei Medical Center, Tainan, Taiwan.
authors: Kuo-Shan
authors: KS
authors: Wen
authors: Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.
authors: Shih-Ting
authors: ST
authors: Hung
authors: Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan.
authors: Lu-Hai
authors: LH
authors: Wang
authors: 1] Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan [2] Department of Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
authors: Kai-Yuan
authors: KY
authors: Lin
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009857:Oncogenes; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics*
chemical_list: D051567:Proto-Oncogene Proteins c-vav; C496621:VAV3 protein, human