Interaction between transcription factors RelA and Stat3 in pancreatic carcinogenesis

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Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a dismal long-term prognosis. Due to the paucity of clinical signs late diagnosis and refractory nature toward treatment, PDAC is one of the eight-leading causes of cancer-related death worldwide and is the second most common cause of death from any type of gastrointestinal disease. In spite of profound advances in surgery, chemo-, and radiation therapy, the prognosis of PDAC remains extremely poor.As mostly ubiquitously expressed transcription factors, proteins of the NF-kB family and Stat3 can control the growth and malignancy of many solid tumors, including pancreatic cancer, via the regulation of expression of a large number of downstream genes that control cell proliferation, survival, stress and immune responses. Some of these genes overlap and require transcriptional cooperation between the two factors. Recent studies have revealed that interaction between Stat3 and NF-kB plays an important role in carcinogenesis and in control of response of the immune system. Although the activation of NF-kB and Stat3 signaling in pancreatic cancer has been shown, the interaction between the NF-kB subunit RelA and Stat3 in PDAC is not completely understood. Thus, we plan to define the molecular mechanisms through which RelA and Stat3 operate and to determine how this knowledge could be exploited for future drug development and clinical applications.