15 Translational Control in Cancer Development and Progression

Abstract

Translational control has an important role in key physiological pathways that have a direct impact on cancer development and progression. These include pathways for cell proliferation and growth, cellular responses to stresses such as hypoxia and nutritional deprivation, and stimulation by mitogenic signals (for previous reviews, see Dua et al. 2001; Meric and Hunt 2002; Rosenwald 2004; Holcik and Sonenberg 2005). Consequently, regulation of protein synthesis has emerged as an important component of cancer etiology, both at the level of global control of the proteome and for selective translation of specific mRNAs and classes of mRNAs. What is surprising is how long it has taken to appreciate the central importance and elucidate the key mechanisms of translational control in cancer development and progression. Despite the infancy of this field of research, it is already apparent that translational control of cancer is multifaceted, presenting modifications unique to different types of cancers, as well as different stages and grades of disease. Changes in translation associated with cancer development and progression observed to date involve altered expression of translation components, including translation factors, ribosomes, translation factor regulatory proteins, and tRNAs; altered expression and translation of specific mRNAs; and altered activity of signal transduction pathways that control the activity of protein synthesis, both overall and of individual mRNAs. These changes are manifested in a variety of ways, including up-regulation of global protein synthesis, increased translation of individual mRNAs, and selective translation of antiapoptotic, proangiogenic, proproliferative, and hypoxia-mediated mRNAs. Other transformation-associated changes in translation are...