VAV3 Oncogene Expression in Colorectal Cancer: Clinical Aspects and Functional Characterization

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...

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Bibliographic Details
Published in:Scientific reports 2015-03, Vol.5 (1), p.9360-9360, Article 9360
Main Authors: Uen, Yih-Huei, Fang, Chia-Lang, Hseu, You-Cheng, Shen, Pei-Chun, Yang, Hsin-Ling, Wen, Kuo-Shan, Hung, Shih-Ting, Wang, Lu-Hai, Lin, Kai-Yuan
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
13/31
13/51
13/89
38/88
38/90
692/308/1892
692/308/575
692/53/2422
82/80
AKT protein
Cell cycle
Clinical aspects
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
Humanities and Social Sciences
Humans
Medical prognosis
Metastases
Metastasis
multidisciplinary
Oncogenes
Proto-Oncogene Proteins c-vav - genetics
Science
Signal transduction
Xenografts
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep09360