Neither macrophage nor endothelial cluster contains TIE2, which has been implicated, based largely upon in vitro studies, in tumour-associated angiogenesis and regulatory T cell production [ 65, 66].
Aurora B and Plk1 have been implicated in chromosome congression upon knockdown of B56 subunits (Foley et al., 2011).
Previously, an autocrine TNF α loop has been implicated to mediate apoptosis upon single agent treatment with cytotoxic concentrations of Smac mimetics that stimulate the production of TNF α, thereby initiating TNFR1-mediated cell death.
Like other FoxOs, FoxO6 has been implicated in the hepatic gluconeogenesis upon fasting by activating the expression of gluconeogenic enzymes, such as PPECK and G6Pase, and which can be blunted by insulin [ 28].
In other organisms mechano-sensitive channels and aquaporins have been implicated in osmoregulation of cell turgor upon osmotic downshift [14], [15].
The EGFR pathway is highly expressed in a variety of solid tumours, including NSCLC, and has been implicated in tumorigenesis through its effects upon cell-cycle progression, apoptosis, angiogenesis, tumour-cell motility and metastasis (Ciardiello and Tortora, 2001; Salomon and Gullick, 2001; Arteaga, 2002; Bunn Jr and Franklin, 2002).
In fact, several TFs predicted to bind to DMRs and differentially expressed genes upon senescence have been implicated in replicative senescence before: EGR1, also known as zinc finger protein 225, has been shown to play a central role in aging [ 51, 52] and replicative senescence [ 53].
Cell adhesion molecules mediating either cell cell interactions or cell matrix adhesion have emerged as key players throughout the natural history of EOC development, in that they have been implicated both in cancer cell survival upon detachment from the primary tumour and in the subsequent adhesion to and invasion of metastatic sites (Naora & Montell, 2005; Sundfeldt, 2003).
Interestingly, this region also has been implicated as the key to folding nucleation upon lipid binding.
