NUCLEAR FACTOR-KAPPAB IN CANCER DEVELOPMENT AND PROGRESSION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 核因子-kappaB(NF-kappaB)转录因子及其激活的信号通路是天然免疫和获得性免疫反应的中心协调者。很明显，核因子-kappaB信号在癌症的发生和发展中也起着关键作用。核因子-kappaB在炎症和癌症之间提供了一种机制上的联系，并且是控制肿瘤前期和恶性细胞抵抗基于凋亡的肿瘤监视机制的能力的主要因素。核因子-kappaB也可能调节肿瘤的血管生成和侵袭性，其激活的信号通路为新的化学预防和化疗方法提供了诱人的靶点。在与炎症相关的癌症中，细胞凋亡(自杀性)和自噬(自食性)之间的功能关系是复杂的，因为在某些情况下，自噬是一种避免细胞死亡并抑制细胞凋亡的应激反应，而在其他情况下，它构成了另一种细胞死亡途径。由于线粒体是细胞凋亡中的关键角色，我们正在使用NCMIR的电子显微镜资源来研究线粒体潜在的结构变化，这些变化指示了与细胞基于凋亡的肿瘤监视机制相关的信号通路。

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.