Autophagy in cancer: The cornerstone during glutamine deprivation

Over the past two decades, researchers have revealed the crucial functions of glutamine in supporting the hyperproliferation state of cancer cells. Glutamine acts on maintaining high energy production, supporting redox status and amino acid homeostasis. Therefore, cancer cells exhibit excessive uptake of the extracellular glutamine, synthesize it in some cases, and recycle intracellular and extracellular proteins to provide an additional source of glutamine to satisfy the increasing glutamine demand. On the other hand, autophagy's role is still debated regarding tumor initiation and progression. However, most cancer cells urgently need autophagy to overcome the existential threats during glutamine restriction stress. Downstream to various stress pathways induced during such a condition, autophagy is considered an indispensable cytoprotective tool to maintain cell integrity and survival. However, the overactivation of the autophagy process is related to lethal consequences. This review summarized glutamine pathways to control autophagy and highlighted autophagy's primary activation pathways, and discussed the roles during glutamine deprivation.