Pancreatic cancer (PanCa) is a significant problem, and its treatment is a major challenge in front of onco-physicians. It shows only marginal survival benefits of 6 months with the available therapeutics. According to the American Cancer Society, PanCa is the third leading cause of cancer-related deaths in the United States. Thus, understanding the biology of PanCa is urgently required. Aberrant ribosome biogenesis is the hallmark of many cancers and has been associated with poor prognosis. Cancer cells show a significantly high demand for protein synthesis and to meet this demand they modify ribosomal machinery to produce onco-ribosomes. Through this project, we for the first time will inv...

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Pancreatic cancer (PanCa) is a significant problem, and its treatment is a major challenge in front of onco-physicians. It shows only marginal survival benefits of 6 months with the available therapeutics. According to the American Cancer Society, PanCa is the third leading cause of cancer-related deaths in the United States. Thus, understanding the biology of PanCa is urgently required. Aberrant ribosome biogenesis is the hallmark of many cancers and has been associated with poor prognosis. Cancer cells show a significantly high demand for protein synthesis and to meet this demand they modify ribosomal machinery to produce onco-ribosomes. Through this project, we for the first time will investigate the role of upstream binding transcription factor (UBTF) in PanCa. Our preliminary results provided some clues about UBTF link to PanCa. We observed high expression of UBTF in human pancreatic tumor tissues and PanCa cells compared to normal adjacent tissues and normal pancreatic ductal epithelial cells. We also observed that targeted knockdown of UBTF significantly (P<0.01) inhibits the expression of mutant p53 (the most frequent mutation in the late stage of PanCa). Based on this compelling evidence, we hypothesize that UBTF is linked to the growth and metastatic phenotypes of PanCa. To prove our hypothesis, we performed various gains of function and loss of function of UBTF in PanCa cells and its impact on pancreatic tumor growth and metastasis in a xenograft mouse model. Overall, this project has significant translational implications because establishing UBTF as a new molecular target will help in developing new therapeutic strategies for the treatment of advanced PanCa. Through this pilot CIPRIT grant application, we will generate solid preliminary data for future NIH/R01 and DOD grant applications. UTRGV is fully committed to providing the matching funds over the 2 years for the successful outcome of this project.

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