STAT1 and STAT3 Transcription Factors in Inflammation-associated Colon Cancer
Inflammation is a strong promoter of colorectal cancer formation. Colorectal tumor cells establish heterotypic interactions with inflammatory cells in the stroma that are important for tumor angiogenesis and invasiveness. Recent studies in genetically mod
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Abstract
Inflammation is a strong promoter of colorectal cancer formation. Colorectal tumor cells establish heterotypic interactions with inflammatory cells in the stroma that are important for tumor angiogenesis and invasiveness. Recent studies in genetically modified mice have identified transcription factors and signaling networks that are implicated in these heterotypic tumor-stroma interactions and modulate preconditions of tumor formation such as chronic inflammation. Here, tumor-promoting and tumor-adverse effects of cytokineactivated transcription factors STAT1 and STAT3 in inflammatory cells and colorectal cancer cells are discussed.
Introduction Colorectal Cancer (CRC) in Humans Colorectal cancer (CRC) originates from the epithelial cells lining the colon or rectum of the gastrointestinal tract and represents the third most common form of cancer worldwide. The histopathological sequence of tumor progression has been well defined which was mainly due to the easy accessibility and the frequent appearance
P. Rampetsreiter Ludwig Boltzmann Institute for Cancer Research (LBICR), W€ahringer Straße 13a, 1090 Vienna, Austria R. Eferl (*) Ludwig Boltzmann Institute for Cancer Research (LBICR), W€ahringer Straße 13a, 1090 Vienna, Austria Institute for Cancer Research, Medical University of Vienna (MUV), Vienna, Austria e-mail: [email protected] Th. Decker and M. M€ uller (eds.), Jak-Stat Signaling: From Basics to Disease, DOI 10.1007/978-3-7091-0891-8_16, # Springer-Verlag Wien 2012
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of this tumor type. The most commonly used staging system is represented by the TNM classification defined by the American Joint Committee on Cancer (AJCC). The criteria used by that classification comprise local invasiveness, presence of lymph node metastases and far distant metastasis. Cancers that invade only the colonic submucosa (TNM stage I) or the muscularis propria (TNM stage II) can be cured with surgery. Prognosis is worse when these cancers spread to regional lymph nodes (TNM stage III) but still >70% are curable by surgery and chemotherapy. However, when cancers form far distant metastases (TNM stage IV), they are usually not curable and chemotherapy can only extend survival (Markowitz and Bertagnolli 2009).
Genetic and Epigenetic Changes in CRC The easy accessibility of CRC biopsy samples that represent different stages of tumor development has greatly facilitated the identification of cell-autonomous tumor-inducing genetic and epigenetic events. At early stages, mutations in adenomatous polyposis coli (Apc) have been identified in ~90% of cases indicating that this gene encodes a tumor suppressor whose deletion is an almost essential event for CRC formation. Apc is also mutated in the germline of patients suffering from the inherited disease FAP (familal adenomatous polyposis coli) that leads to development of thousands of adenomatous polyps in the colon thereby increasing the risk for development of CRC substantially (de Lau et al. 2007). Apc encodes a protein that
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