All roads lead to mTOR - Integrating inflammation and tumor angiogenesis

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. Tumor-associated 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 TAMs-induced tumor angiogenesis. Recently IKK beta 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.