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Akt-dependent and -independent mechanisms of mTOR regulation in cancer.

Publication ,  Journal Article
Memmott, RM; Dennis, PA
Published in: Cell Signal
May 2009

The protein kinase mTOR (mammalian target of rapamycin) is a critical regulator of cellular metabolism, growth, and proliferation. These processes contribute to tumor formation, and many cancers are characterized by aberrant activation of mTOR. Although activating mutations in mTOR itself have not been identified, deregulation of upstream components that regulate mTOR are prevalent in cancer. The prototypic mechanism of mTOR regulation in cells is through activation of the PI3K/Akt pathway, but mTOR receives input from multiple signaling pathways. This review will discuss Akt-dependent and -independent mechanisms of mTOR regulation in response to mitogenic signals, as well as its regulation in response to energy and nutrient-sensing pathways. Preclinical and clinical studies have demonstrated that tumors bearing genetic alterations that activate mTOR are sensitive to pharmacologic inhibition of mTOR. Elucidation of novel pathways that regulate mTOR may help identify predictive factors for sensitivity to mTOR inhibitors, and could provide new therapeutic targets for inhibiting the mTOR pathway in cancer. This review will also highlight pharmacologic approaches that inhibit mTOR via activation of the AMP-activated protein kinase (AMPK), an important inhibitor of the mTOR pathway and an emerging target in cancer.

Duke Scholars

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Published In

Cell Signal

DOI

EISSN

1873-3913

Publication Date

May 2009

Volume

21

Issue

5

Start / End Page

656 / 664

Location

England

Related Subject Headings

  • TOR Serine-Threonine Kinases
  • Signal Transduction
  • Proto-Oncogene Proteins c-akt
  • Protein Kinases
  • Protein Kinase Inhibitors
  • Phosphatidylinositol 3-Kinases
  • Neoplasms
  • Mice
  • Biochemistry & Molecular Biology
  • Animals
 

Citation

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Memmott, R. M., & Dennis, P. A. (2009). Akt-dependent and -independent mechanisms of mTOR regulation in cancer. Cell Signal, 21(5), 656–664. https://doi.org/10.1016/j.cellsig.2009.01.004
Memmott, Regan M., and Phillip A. Dennis. “Akt-dependent and -independent mechanisms of mTOR regulation in cancer.Cell Signal 21, no. 5 (May 2009): 656–64. https://doi.org/10.1016/j.cellsig.2009.01.004.
Memmott RM, Dennis PA. Akt-dependent and -independent mechanisms of mTOR regulation in cancer. Cell Signal. 2009 May;21(5):656–64.
Memmott, Regan M., and Phillip A. Dennis. “Akt-dependent and -independent mechanisms of mTOR regulation in cancer.Cell Signal, vol. 21, no. 5, May 2009, pp. 656–64. Pubmed, doi:10.1016/j.cellsig.2009.01.004.
Memmott RM, Dennis PA. Akt-dependent and -independent mechanisms of mTOR regulation in cancer. Cell Signal. 2009 May;21(5):656–664.
Journal cover image

Published In

Cell Signal

DOI

EISSN

1873-3913

Publication Date

May 2009

Volume

21

Issue

5

Start / End Page

656 / 664

Location

England

Related Subject Headings

  • TOR Serine-Threonine Kinases
  • Signal Transduction
  • Proto-Oncogene Proteins c-akt
  • Protein Kinases
  • Protein Kinase Inhibitors
  • Phosphatidylinositol 3-Kinases
  • Neoplasms
  • Mice
  • Biochemistry & Molecular Biology
  • Animals