The RASSF1A Tumor Suppressor Regulates a Cascade of Oncogenic Signals That Are Restrained by G1 Checkpoint Mechanisms
Ram, Rosalyn Ruanga
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The RASSF1A tumor suppressor is one of the most commonly inactivated genes in cancer. To understand why epigenetic silencing of RASSF1A promotes tumorigenesis, I employed a loss of function approach to elucidate the role of RASSF1A in cancer. RASSF1A is reported to regulate apoptosis, cell cycle progression, and microtubule dynamics. Disruption of these processes by RASSF1A loss may disrupt cellular integrity and promote oncogenesis. I found that RASSF1A depletion elevated oncogenic signaling pathways; however, RASSF1A depletion also induced cell cycle arrest. RASSF1A is a critical regulator in maintaining the balance between pro-growth and anti-growth signals. RASSF1A suppresses proliferative signaling pathways such as the MAPK pathway, promotes apoptosis through MST2, but paradoxically, promotes G1/S progression through modulation of the ubiquitin ligase SCF-BTrCP. Thus, RASSF1A represents a critical line of defense against tumorigenesis as its loss triggers cell arrest; however, loss of RASSF1A also promotes proliferative signaling events, and additional malfunctions in cell cycle regulation will likely drive tumorigenesis.