Clinical Significance of Increased Guanine Nucleotide Exchange Factor Vav3 Expression in Human Gastric Cancer

Abstract

Although gastric cancer is one of the most common malignancies worldwide, little is known on the molecular process of its development and progression. This study investigates the involvement of guanine nucleotide exchange factor Vav3 in tumor progression and in the prognosis of human gastric cancer. The two patient cohorts in this study consisted of 167 gastric cancer cases from 1997 through 2001, documenting pathologic and clinical factors, as well as the clinical outcomes. Immunohistochemistry, reverse transcription PCR, immunoblotting, and immunofluorescence were used to examine Vav3 expression in tumor and nontumor pairs of gastric tissues and gastric cell lines. Small hairpin RNA (shRNA) technology was used to study the effects of Vav3 knockdown on the growth and spread of gastric cancer cells. Finally, xenograph proliferation was used to study the tumor growth. Overexpression of Vav3 was associated with the depth of invasion (P ¼ 0.0004), nodal status (P ¼ 0.0260), distant metastasis (P ¼ 0.0003), stage (P ¼ 0.0002), and vascular invasion (P ¼ 0.0286); and correlated with poor disease-free survival (P < 0

Rho guanine nucleotide exchange factors: regulators of Rho GTPase activity in development and disease

“…125 High Vav3 protein expression was associated with disease progression and reduced survival, whereas RNAi depletion reduced the tumorigenic and metastatic growth of androgen-independent prostate tumor cells. 128 Finally, suppression of Vav3 expression enhanced docetaxel-induced apoptosis in prostate cancer cells, further supporting a therapeutic value in blocking Vav3 function in prostate cancer. 129 …”

VAV3 Overexpressed in Cancer Stem Cells Is a Poor Prognostic Indicator in Ovarian Cancer Patients

“…Of the three VAV proteins, VAV3 reportedly plays an important role in tumor development and metastasis [33]. Previous reports demonstrated that VAV3 overexpression was associated with poor prognosis in gastric cancer patients [34], and VAV3 knockdown impaired carcinogenesis in leukemia and gastric cancer [34,35]; however, VAV3 expression in ovarian cancer has not yet been reported. In the present study, we revealed that VAV3 was overexpressed in OSCs, and VAV3 regulated CSC activation and cancer cell proliferation by spheroid-forming and colony-forming assays.…”

Novel Interaction between the Co-chaperone Cdc37 and Rho GTPase Exchange Factor Vav3 Promotes Androgen Receptor Activity and Prostate Cancer Growth*

“…Vav3 may also participate in other human cancers (12)(13)(14)(15). Vav3 overexpression is correlated with poor differentiation of breast cancer and is a predictor of decreased survival in patients with glioblastoma (12).…”

“…Vav3 also plays a role in the development of anaplastic large cell lymphomas (13). Vav3 is up-regulated in human gastric cancer, and Vav3 overexpression is inversely correlated with gastric cancer patient survival (14).…”