The Cytokine Signaling, Inflammation, and Cancer focus group includes investigators with interests in innate immune signaling pathways that lead to inflammatory responses and cancer. Included are studies of cytokines (TGFβ, interferons), Toll-like receptors (TLRs), and key stress-inducible transcription factors (STATs, NFκB).
This focus group brings together basic and physician scientists with a common interest in TGFβ signaling and a shared goal to define the complex roles of this pathway in disease pathogenesis and carcinogenesis. During the earliest stages of carcinogenesis TGFβ principally functions as a tumor suppressor. However, during later stages of disease, biologically active TGFβ, often produced by cancer cells, can aid tumor growth and metastasis through its ability to suppress immune cells, enhance angiogenesis, promote matrix production and induce cancer cell migration. At late times, most tumors become refractory to the growth inhibitory effects of the cytokine, often through mechanisms involving the down-regulation of expression of TGFβ receptors at the cell surface.
TLRs, key components in generating immune and inflammatory responses, recognize pathogen-associated molecules, leading to the production of pro-inflammatory cytokines, which further up-regulate the expression of inflammatory genes at both transcriptional and posttranscriptional levels. While the TLR- and cytokine-mediated inflammatory responses are critical for innate immunity and host defense against infections, uncontrolled inflammation is detrimental to the host, leading to chronic inflammatory diseases. It is now commonly accepted that chronic inflammation contributes to tumor promotion and progression. New insight about TLR- and cytokine-mediated regulatory mechanisms can lead to strategies to limit the production of harmful toxins, resulting in better resolution of inflammatory diseases. Activation of TLRs leads to activation of NFκB and production of type I interferons, which are additional major topics within the focus group.
Signal transduction is the process through which stimuli in the external milieu of a cell are first detected by a cell surface receptor, and then interpreted within the cell, through a series of biochemical events, resulting most often in changes in gene expression. STATs and NFκB transmit this information, and their dysregulation can contribute to cell transformation and unregulated cell growth. The STATs function as transcription factors in response to a wide range of environmental stimuli, including the interferon family of cytokines. Members of this focus group investigate the function of STATs family tumorigenesis and in the setting of inflammatory stimulation of carcinogenesis.
Ernest C. Borden, MD
Professor, Translational Hematology and Oncology Research
Ge Jin, PhD
Assistant Professor, Biological Sciences