The invention provides cell-permeable Ga-Interacting Vesicle associated protein (GIV)-derived peptides and their use for treatment of diverse diseases. The invention further provides C-terminus of Ga-Interacting Vesicle associated protein (GIV-CT)-based peptides and GIV-CT encoding vectors and methods of use thereof, for successfully manipulating the diverse pathophysiologic processes in which GIV has been implicated. In one aspect, the invention provides cell-permeable peptides PTD-GIV-CT comprising (i) a peptide transduction domain (PTD) and (ii) a C-terminus of Ga-Interacting Vesicle associated protein (GIV-CT) or a mutant thereof. In one embodiment, said peptides are capable of activating Gi downstream of receptor tyrosine kinases (RTKs). The invention also provides pharmaceutical compositions comprising one or more of the peptides of the invention as well as vectors encoding such peptides.