Does Autophagy Promote or Suppress Cancers? Is it both?
Jun 29, 2022 | Written By Sophia Mai
Have you ever fasted or gone long periods where you haven’t eaten? This process is autophagy, and doing this in moderation can help clean your body of harmful toxins and substances. Autophagy is reported to have anti-aging properties and is a way for the body to clean out damaged cells to regenerate new, healthier ones. Throughout the lifespan of cells, they are exposed to various stressors that affect their homeostasis.
What is Autophagy?
“Auto” means self, while “phagy” means eat. Autophagy is the self-eating or the self-degradation of damaged cells that induces autophagosome formation to take damaged materials to the lysosome. It is an important cell survival mechanism that allows cells to adapt to development and stressors such as nutrient deficiencies, starvation, damage, hypoxia, and infection by repurposing damaged materials in the cell as energy. Autophagy is a recycling process that provides the necessary nutrients during a vulnerable time by breaking down cellular material such as misfolded proteins and damaged organelles. This process also helps maintain cell homeostasis and protects cells against pathogens or harmful bacteria that have accessed the cell and into the cytoplasm. When cells are stressed, autophagy increases to protect the body by breaking down cellular materials and promoting the development of healthier cells.
Under normal circumstances, autophagy is used at the bottommost levels to assist in the maintenance of the cell, for example, maintaining homeostasis and cleaning damaged organelles and proteins.
Autophagy affects both tumor suppression and production and affects these depending on the type of cancer and how advanced the cancer is. Defects of autophagy can be linked to genetic damage, metabolic stress, and oncogenesis (development of tumors). Autophagy can prevent tumor production in cancer cells by inhibiting cancer-cell survival and causing cell death. However, it can also induce tumorigenesis by causing cancer-cell growth. Autophagy plays a dual role in tumor suppression and tumor production. Certain anticancer drugs regulate autophagy, and therefore, chemotherapies that regulate autophagy can be involved in cancer survival or death.
Image Credits: https://www.verywellhealth.com/how-autophagy-works-4210008
How does Autophagy suppress tumors?
In the early stages of tumorigenesis, autophagy is a tumor suppressor by degrading oncogenic molecules, reducing damaged parts, and cellular maintenance. Various studies show that a decrease of the autophagy-related gene BECN1 is seen in a variety of cancers such as breast, prostate, and ovarian cancers. However, this gene is important for creating phagophores suggesting that Beclin 1 suppresses tumors. The loss of Beclin 1 reduced autophagy and increased cancer-cell growth in mice showing that this gene acts as a suppressor. Autophagy prevents tumor production through regulating reactive oxygen species (ROS) which is created as a byproduct of mitochondrial metabolism. Damage to mitochondria induces ROS production promoting tumorigenesis. Autophagy is crucial for inhibiting tumor production; however, weakened autophagy can result in tumor production.
How does autophagy promote tumors?
In later stages of cancer production, autophagy promotes the production and survival of tumor cells. Reduced and abnormal autophagy prevents the degradation of damaged components and proteins in cells in unfavorable conditions that can lead to the development of cancer. Mutations of certain proteins called UVRAG reduces autophagy resulting in an increase in cancer-cell growth in cancer cells. Tumors are also exposed to numerous unfavorable conditions such as nutrient deficiencies, and autophagy helps the cancer-cells overcome the stressors. Autophagy provides cancer-cells with high energy demands of growing tumors by recycling cellular material. Autophagy can contribute to tumor cell survival by strengthening stress tolerance and providing nutrients to the tumor.
Image Credits: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274804
Why Is Autophagy Important?
Autophagy plays a vital role in embryonic development and maintaining healthy cell survival, and homeostasis. Autophagy prevents DNA damage and the production of reactive oxygen species (ROS), promotes cell survival, and regulates cellular metabolic state. Reactive oxygen species are unstable molecules that can easily react with other molecules in a cell. Oxidative stress is the accumulation of ROS in cells, and the imbalance of the oxygen species and oxidants can cause damage to the DNA, and RNA, and increase tumorigenesis. Reactive oxygen species are produced as a byproduct during mitochondrial metabolism which is when mitochondria produce ATP or energy for processes in living cells. Reactive oxygen species are also generated in response to bacterial invasion and foreign substances in the body. Oxidative stress is in various diseases such as cancers and aging and autophagy helps maintain the levels of ROS in cells.
Cancer will be a constant struggle for society but by looking at the smaller details and questioning, we may be one step closer to figuring out the solutions.
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