NUCLEAR FACTOR-KAPPAB IN CANCER DEVELOPMENT AND PROGRESSION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Nuclear factor-kappaB (NF-kappaB) transcription factors and the signaling pathways that activate them are central coordinators of innate and adaptive immune responses. It has become clear that NF-kappaB signaling also has a critical role in cancer development and progression. NF-kappaB provides a mechanistic link between inflammation and cancer, and is a major factor controlling the ability of both pre-neoplastic and malignant cells to resist apoptosis-based tumor-surveillance mechanisms. NF-kappaB might also regulate tumor angiogenesis and invasiveness, and the signaling pathways that mediate its activation provide attractive targets for new chemopreventive and chemotherapeutic approaches. With inflammation-linked cancers, the functional relationship between apoptosis ('self-killing') and autophagy ('self-eating') is complex because under certain circumstances, autophagy is a stress response that avoids cell death and suppresses apoptosis, whereas under other conditions, it constitutes an alternative cell-death pathway. Because mitochondria are key players in apoptosis, we are using the electron microscopy resources of NCMIR to investigate potential structural changes to mitochondria indicative of signaling pathways related to a cell's apoptosis-based tumor-surveillance mechanisms.