All roads lead to mTOR: integrating inflammation and tumor angiogenesis

Cell Cycle. 2007 Dec 15;6(24):3011-4. doi: 10.4161/cc.6.24.5085. Epub 2007 Sep 20.


Mammalian target of rapamycin (mTOR) is a crucial molecule in the control of cell size and proliferation; dysregulation of the mTOR pathway is commonly found in human cancers. Many cancer-promoting kinases have been identified as regulators of mTOR activity through phosphorylation and inactivation of the TSC1-TSC2 complex. Tumorassociated macrophages (TAMs) are tumor-promoting factors in inflammation-mediated tumor development, and the signaling molecules involved in TAMs-mediated tumor angiogenesis are not well understood. Therefore, it is urgent to elucidate the cross-talk between inflammatory cells and cancers and to explore the precise pathways involved in TAMsinduced tumor angiogenesis. Recently IKKbeta was found to activate the mTOR pathway and to promote tumor angiogenesis through inactivation of the TSC1-TSC2 complex by phosphorylating TSC1. This finding provides critical insights into and suggests one mechanism behind inflammation-mediated tumor angiogenesis. In this extra-view, we briefly discuss the possible influence of TAMs-released proangiogenic factors on mTOR activation and propose a model of the cross-talk between tumors and TAMs in tumor angiogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Humans
  • I-kappa B Kinase / metabolism
  • Neoplasms / blood supply*
  • Neoplasms / metabolism*
  • Neovascularization, Pathologic / metabolism*
  • Phosphorylation
  • Protein Kinases / physiology*
  • Signal Transduction
  • TOR Serine-Threonine Kinases
  • Tuberous Sclerosis Complex 1 Protein
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins / metabolism


  • TSC1 protein, human
  • TSC2 protein, human
  • Tuberous Sclerosis Complex 1 Protein
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • I-kappa B Kinase