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Both mTORC1 and mTORC2 are involved in the regulation of cell adhesion

Long Chen1,2, Baoshan Xu2, Lei Liu2

  • 1Jiangsu Key Laboratory for Microbes and Functional Genomics, Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, P. R. China.

Oncotarget
|March 13, 2015
PubMed

Insights

The mechanistic target of rapamycin (mTOR) pathway regulates cancer cell adhesion. Both mTORC1 and mTORC2 complexes are involved, with mTORC1 signaling through S6K1 and 4E-BP1, and mTORC2 acting independently of Akt.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • The mechanistic target of rapamycin (mTOR) is a key regulator of cell growth, proliferation, and survival.
  • Emerging evidence suggests mTOR's involvement in cell adhesion, but the underlying molecular mechanisms remain unclear.

Purpose of the Study:

  • To elucidate the role and mechanisms of mTOR in regulating cancer cell adhesion.
  • To determine the specific contributions of mTORC1 and mTORC2 complexes to cell adhesion regulation.

Main Methods:

  • Inhibition of mTOR signaling using rapamycin and PP242.
  • Genetic manipulation including silencing of raptor/rictor, ectopic expression of S6K1/4E-BP1 mutants, and Akt manipulation.
  • Assessment of basal and IGF-1-stimulated cancer cell adhesion.

Main Results:

  • mTOR inhibition by rapamycin reduced cancer cell adhesion.
  • Both mTORC1 and mTORC2 complexes were implicated, as evidenced by reduced adhesion upon raptor/rictor silencing.
  • PP242 demonstrated more potent inhibition of cell adhesion than rapamycin.
  • mTORC1-mediated adhesion involves S6K1 and 4E-BP1 pathways, while mTORC2 acts via an Akt-independent mechanism.

Conclusions:

  • Both mTORC1 and mTORC2 are critical regulators of cancer cell adhesion.
  • mTORC1 controls cell adhesion through the S6K1 and 4E-BP1 signaling pathways.
  • mTORC2 regulates cell adhesion independently of the Akt pathway.
Keywords:
4E-BP1Aktcell adhesionmTORrapamycin

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