VAV3 oncogene expression in colorectal cancer: clinical aspects and functional characterization

Yih Huei Uen, Chia-Lang Fang, You Cheng Hseu, Pei Chun Shen, Hsin Ling Yang, Kuo Shan Wen, Shih Ting Hung, Lu Hai Wang, Kai Yuan Lin

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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.

Original languageEnglish
Pages (from-to)9360
Number of pages1
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - 2015

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Uen, Y. H., Fang, C-L., Hseu, Y. C., Shen, P. C., Yang, H. L., Wen, K. S., Hung, S. T., Wang, L. H., & Lin, K. Y. (2015). VAV3 oncogene expression in colorectal cancer: clinical aspects and functional characterization. Scientific Reports, 5, 9360. https://doi.org/10.1038/srep09360