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Review
. 2022 Feb;61(2):243-253.
doi: 10.1002/mc.23372. Epub 2021 Nov 15.

Autophagy awakens-the myriad roles of autophagy in head and neck cancer development and therapeutic response

Samantha T Bradley  1 , Yong-Syu Lee  1 , Zafer Gurel  1 , Randall J Kimple  1   2
Affiliations
Review

Autophagy awakens-the myriad roles of autophagy in head and neck cancer development and therapeutic response

Samantha T Bradley et al. Mol Carcinog. 2022 Feb.

Abstract

Autophagy is an evolutionarily conserved cell survival mechanism that degrades damaged proteins and organelles to generate cellular energy during times of stress. Recycling of these cellular components occurs in a series of sequential steps with multiple regulatory points. Mechanistic dysfunction can lead to a variety of human diseases and cancers due to the complexity of autophagy and its ability to regulate vital cellular functions. The role that autophagy plays in both the development and treatment of cancer is highly complex, especially given the fact that most cancer therapies modulate autophagy. This review aims to discuss the balance of autophagy in the development, progression, and treatment of head and neck cancer, as well as highlighting the need for a deeper understanding of what is still unknown about autophagy.

Keywords: autophagy; cancer; chemotherapy; radiation.

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest with the included work to disclose.

Figures

Figure 1.
Figure 1.. Types of autophagy.
There are three major types of autophagy. a) Macroautophagy involves the fusion of the autophagosome and lysosome to degrade damaged cytosolic cargos. Autophagy can occur either via non-selective (bulk) degradation or through selective elimination of cytosolic components including different dysfunctional organelles such as mitochondria and ribosomes. b) Chaperone-mediated autophagy (CMA) occurs independent of the autophagosome and lysosomal invagination. Chaperone proteins, such as Hsc70, recognize cytosolic cargo destined by degradation by their consensus sequence known as the KFERQ-like motif. c) Microautophagy is the process where lysosomes directly engulf cytosolic components via invagination of the lysosomal membrane.
Figure 2.
Figure 2.. Cellular stress-induced autophagy.
Autophagy induction can be mediated by the AMPK-mTOR pathway in response to various cellular stresses, such as starvation, hypoxia, amino acid depletion, energy depletion and stress. Once mTOR has been inhibited, the downstream Ulk1 and Vps34 complex will be activated and then further initiate autophagy maturation.
Figure 3.
Figure 3.. Signaling pathway of autophagy and autophagy inhibitors.
Activated Vps34 complex cooperates with the Atg5/12/16 complex and LC3II to maturate autophagosomes. Damaged proteins or organelles labeled with p62 are engulfed in autophagosomes and ultimately fuse with lysosomes for degradation or recycling. Several inhibitors have been developed (purple boxes) to suppress autophagy at different steps.
Figure 4.
Figure 4.. The role of autophagy in tumorigenesis.
Autophagy acts to protect healthy cells from malignant transformation. Once the malignancy has been established, the loss of autophagy has been proposed as a biomarker for the initiation of early-stage cancers. As tumors progress, autophagy becomes a cellular protector to help cancer grow and survive in a resource-limited microenvironment.
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References

    1. Parzych KR, Klionsky DJ. An Overview of Autophagy: Morphology, Mechanism, and Regulation. Antioxidants & Redox Signaling. 2014. Jan 20;20(3):460–73. - PMC - PubMed
    1. Thorburn A, Thamm DH, Gustafson DL. Autophagy and Cancer Therapy. Mol Pharmacol. 2014. Jun;85(6):830–8. - PMC - PubMed
    1. Jin M, Liu X, Klionsky DJ. SnapShot: Selective autophagy. Cell. 2013. Jan 17;152(1–2):368–368.e2. - PMC - PubMed
    1. Li W, Li J, Bao J. Microautophagy: lesser-known self-eating. Cell Mol Life Sci. 2012. Apr;69(7):1125–36. - PMC - PubMed
    1. Nixon RA. Autophagy, amyloidogenesis and Alzheimer disease. Journal of Cell Science. 2007. Dec 1;120(23):4081–91. - PubMed

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