Abstract
Introduction Nuclear factor-κB (NF-κB) transcription factors and their signaling pathways have come to the forefront of the cancer field as mechanistic links connecting chronic inflammation and oncogenesis (1). These master transcription factors integrate multiple stimuli and co-ordinate innate and adaptive immune responses involved in acute and chronic inflammation (2). Epidemiological studies which pointed out that chronic inflammation and persistent infections greatly increase the risk of cancers of stomach, colon, and liver first suggested a link between inflammation, the innate immune response, and cancer (3). NF-κB was suggested as the molecular culprit that bridges these pathophysiological states and responses (1). However, establishing the association between NF-κB signaling and oncogenesis has been a challenging task because NF-κB and its activating machinery are rarely mutated in cancer cells in the same way as classical oncogenes (like Ras) or tumor-suppressor genes (like p53). Nonetheless, much evidence has been gathered, both through correlative studies and through direct experimentation, that NF-κB signaling does indeed contribute to cancer development and progression, mainly in inflammation-associated cancers, but also in cancers where underlying chronic inflammation plays little or no role (for example, breast and prostate cancers). The list of human cancers that were found to exhibit constitutive NF-κB activation is long (see Table 29.1). Experimental evidence providing causality for NF-κB signaling in oncogenesis has accumulated over the past several years (4), and will be detailed in this chapter.
Original language | English (US) |
---|---|
Title of host publication | Molecular Oncology |
Subtitle of host publication | Causes of Cancer and Targets for Treatment |
Publisher | Cambridge University Press |
Pages | 336-352 |
Number of pages | 17 |
ISBN (Electronic) | 9781139046947 |
ISBN (Print) | 9780521876629 |
DOIs | |
State | Published - Jan 1 2015 |
ASJC Scopus subject areas
- General Medicine