Elimination of cancer stem cells and reactivation of latent HIV-1 via AMPK activation: Common mechanism of action linking inhibition of tumorigenesis and the potential eradication of HIV-1

摘要: Although promising treatments are currently in development to slow disease progression and increase patient survival, cancer remains the second leading cause of death United States. Cancer treatment modalities commonly include chemoradiation therapies that target components aberrantly activated signaling pathways. However, resistance is a common occurrence recent evidence indicates existence stem cells (CSCs) may underlie limited efficacy inability current effectuate cure. CSCs, which largely resistant therapy, subpopulation exhibit characteristics similar embryonic (ESCs), including self-renewal, multi-lineage differentiation, ability initiate tumorigenesis. Interestingly, intracellular mechanisms sustain quiescence promote self-renewal adult (ASCs) CSCs likely also function maintain latency HIV-1 CD4+ memory T cells. antiretroviral therapy highly effective controlling replication, persistence latent but replication-competent proviruses necessitates compounds capable selectively reactivating virus, method known as "shock kill" approach. Homeostatic proliferation central (TCM) cells, cell subset exhibits differentiation primary reservoir for HIV-1, has been shown reinforce stabilize absence activation differentiation. found establish durable long-lasting recently discovered (TSCM) TSCM compared TCM properties more closely match those ESCs ASCs, into all subsets. It our hypothesis AMPK, master regulator cellular metabolism plays critical role will lead both activation-induced reactivation, facilitating virus destruction, well "activation", and/or apoptosis thus inhibiting We propose novel observation have facilitate reactivation CSC differentiation/apoptosis (e.g. bryostatin-1, JQ1, metformin, butyrate, etc.) do so through mechanism AMPK activation.