Ayman Khatib

Ayman Khatib, University of Central Florida

Frabin, a RhoGEF, Promotes Pancreatic Cancer Progression

Pancreatic cancer (PCa) is the third leading cause of cancer-related deaths in the United States with a five-year survival rate of only 8%. Activation of Cdc42 in RhoGTPase pathways is shown to be involved in PCa progression and metastasis. Frabin (FGD4) is a Guanine Nucleotide Exchange Factor that activates Cdc42 and has an actin-binding domain which might contribute to tumor metastasis. PCa analysis of clinical samples from The Cancer Genome Atlas database (TCGA) showed FGD4 to be upregulated in pancreatic tumors compared to normal tissues. Survival analysis showed an inverse relationship between patient longevity and FGD4 expression. Here we show that ectopic expression of FGD4 in the less aggressive PANC-1 cell increased cell proliferation and cell cycle progression. Quantitative RT-PCR analysis was used to confirm the overexpression of FGD4 in PANC-1 cells. MTS assays showed a 35% increase in cell proliferation upon overexpression of FGD4. Cell cycle analysis revealed an increased percentage of cells in the S phase in the FGD4 expressing cells compared to control cells. These initial results suggest an oncogenic involvement of FGD4 in PCa. Further studies using overexpression and knockdown approaches will explore the role of FGD4 on cell migration and drug sensitivity in PCa cell lines. We expect that the results of this study will help to determine the function of FGD4 in PCa development and to identify a molecular marker and a therapeutic target for aggressive PCa.

Biography