Research on thyroid cancer has elucidated the theory that paracrine signaling may aid in creating tumor microenvironments.  Chemokine transcription is upregulated when Ras is in the GTP-bound state.  The chemokines are then released from the cell, free to bind to another nearby cell.  Paracrine signaling between neighboring cells creates this positive feedback loop.  Thus, the constitutive transcription of upregulated proteins form ideal environments for tumors to arise.  Effectively, multiple bindings of ligands to the RTK receptors overstimulates the Ras-Raf-MAPK pathway, which overexpresses the mitogenic and invasive capacity of cells.