RKIP & GSK3β: The interaction of two intracellular signaling network regulators and their role in cancer

RKIP is a prominent metastasis suppressor protein and independent prognostic marker, known for its ability to subdue oncogenic proliferation, EMT progression, migration and survival. Current knowledge of the RKIP's ability to maintain the activity of GSK3β signaling cascade, highlights an important mechanism through which RKIP orchestrates cancer behavior and therapeutic outcome. Both RKIP and GSK3β are master regulators in the sense of their ability to modulate many cellular signaling networks. Their aberrant regulation impacts cancer course, fate and responsiveness to chemotherapy and radiotherapy. Downstream effector molecules of both RKIP and GSK3β possess either pro-tumorigenic or anti-tumorigenic properties. Here, we navigate through RKIP and GSK3β's individual and intersecting signaling circuitries and regulatory consequences on cancer progression and treatment. It is arguable, that increasing RKIP expression is an attractive therapeutic model that aims to enhance the antitumor and pro-chemosensitive effects of GSK3β in a tissue-specific manner and in certain cancer scenarios.