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Cyclin D1, Metabolism, and the Autophagy-Senescence Balance

  • Claudio Valenzuela
  • Nelson E. BrownEmail author
Chapter
Part of the Current Cancer Research book series (CUCR)

Abstract

Progression through the cell cycle must be coordinated with crucial cell fate decisions, including the ability of a cell to exit the cell cycle and differentiate. Not surprisingly, deregulation of the G1/S transition is a well-established hallmark of cancer. While the basic mechanisms involved in this transition have been extensively characterized, it is now evident that components of the core cell cycle machinery, including cyclin D1, are functionally integrated into complex signaling and metabolic pathways not always directly related to cell cycle. In cells at risk of becoming cancerous, this complexity may underlie the cellular variability in the specific tumor suppressive processes that are implemented in response to oncogenic insults. Among these processes, autophagy has generated much debate because it may serve both as a tumor suppressive and as a pro-survival mechanism depending on the stage of tumor formation or the cell type under scrutiny. Nevertheless, a better understanding of the role of autophagy in tumorigenesis, and the functional connection of autophagy with the cell cycle and the metabolic status of the cell, may be necessary for the implementation of more rational regimens to treat cancer. In particular, recent reports have begun to unravel cyclin D1’s involvement in the regulation of the autophagy-senescence balance, as well as the role of cyclin D1 function in metabolic responses. The emerging picture is concordant with the idea that cyclin D1 participates in the integration and transduction of inputs provided by both growth factors and metabolic substrates. The proper integration of these signals, in turn, may be necessary to achieve an appropriate proliferative response. To what extent these functions are exclusively dependent on cyclin D1’s ability to bind and activate CDK4/CDK6, however, remains unclear.

Keywords

Cell cycle Autophagy Metabolism Cyclin D1 Senescence 

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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Center for Medical Research, University of Talca School of MedicineTalcaChile

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