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Metabolic Reprogramming by the PI3K-Akt-mTOR Pathway in Cancer.

Date Posted: February 8, 2017

TitleMetabolic Reprogramming by the PI3K-Akt-mTOR Pathway in Cancer.
Publication TypeJournal Article
Year of Publication2016
AuthorsLien EC, Lyssiotis CA, Cantley LC
JournalRecent Results Cancer Res
Volume207
Pagination39-72
Date Published2016
ISSN0080-0015
Abstract

In the past decade, there has been a resurgence of interest in elucidating how metabolism is altered in cancer cells and how such dependencies can be targeted for therapeutic gain. At the core of this research is the concept that metabolic pathways are reprogrammed in cancer cells to divert nutrients toward anabolic processes to facilitate enhanced growth and proliferation. Importantly, physiological cellular signaling mechanisms normally tightly regulate the ability of cells to gain access to and utilize nutrients, posing a fundamental barrier to transformation. This barrier is often overcome by aberrations in cellular signaling that drive tumor pathogenesis by enabling cancer cells to make critical cellular decisions in a cell-autonomous manner. One of the most frequently altered pathways in human cancer is the PI3K-Akt-mTOR signaling pathway. Here, we describe mechanisms by which this signaling network is responsible for controlling cellular metabolism. Through both the post-translational regulation and the induction of transcriptional programs, the PI3K-Akt-mTOR pathway coordinates the uptake and utilization of multiple nutrients, including glucose, glutamine, nucleotides, and lipids, in a manner best suited for supporting the enhanced growth and proliferation of cancer cells. These regulatory mechanisms illustrate how metabolic changes in cancer are closely intertwined with oncogenic signaling pathways that drive tumor initiation and progression.

DOI10.1007/978-3-319-42118-6_3
Alternate JournalRecent Results Cancer Res.
PubMed ID27557534
Grant ListR01 GM041890 / GM / NIGMS NIH HHS / United States