Autophagic Cell Death and Cancer

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2014 Feb 26

PMID 24566140

Citations 108

Authors

Shigeomi Shimizu

Tatsushi Yoshida

Masatsune Tsujioka

Satoko Arakawa

Affiliations

Soon will be listed here.

Abstract

Programmed cell death (PCD) is a crucial process required for the normal development and physiology of metazoans. The three major mechanisms that induce PCD are called type I (apoptosis), type II (autophagic cell death), and type III (necrotic cell death). Dysfunctional PCD leads to diseases such as cancer and neurodegeneration. Although apoptosis is the most common form of PCD, recent studies have provided evidence that there are other forms of cell death. One of such cell death is autophagic cell death, which occurs via the activation of autophagy. The present review summarizes recent knowledge about autophagic cell death and discusses the relationship with tumorigenesis.

Citing Articles

Valproic Acid Enhances Venetoclax Efficacy in Targeting Acute Myeloid Leukemia.

Kawakatsu R, Tadagaki K, Yamasaki K, Kuwahara Y, Yoshida T Diseases. 2025; 13(1).

PMID: 39851474 PMC: 11764158. DOI: 10.3390/diseases13010010.

Different Cytotoxic Effects of Cisplatin on Pancreatic Ductal Adenocarcinoma Cell Lines.

Muscella A, Cossa L, Stefano E, Rovito G, Benedetti M, Fanizzi F Int J Mol Sci. 2025; 25(24.

PMID: 39769425 PMC: 11727771. DOI: 10.3390/ijms252413662.

The Role of Bcl-2 Family Proteins and Sorafenib Resistance in Hepatocellular Carcinoma.

de Melo Silva A, de Melo Gama J, de Oliveira S Int J Cell Biol. 2024; 2024:4972523.

PMID: 39188653 PMC: 11347034. DOI: 10.1155/2024/4972523.

RBBP4: A novel diagnostic and prognostic biomarker for non-small-cell lung cancer correlated with autophagic cell death.

Zhan Y, Zhang Z, Yin A, Su X, Tang N, Chen Y Cancer Med. 2024; 13(15):e70090.

PMID: 39109577 PMC: 11304277. DOI: 10.1002/cam4.70090.

Hepatocyte programmed cell death: the trigger for inflammation and fibrosis in metabolic dysfunction-associated steatohepatitis.

Cheng Z, Chu H, Seki E, Lin R, Yang L Front Cell Dev Biol. 2024; 12:1431921.

PMID: 39071804 PMC: 11272544. DOI: 10.3389/fcell.2024.1431921.

References

Iqbal J, Kucuk C, Deleeuw R, Srivastava G, Tam W, Geng H . Genomic analyses reveal global functional alterations that promote tumor growth and novel tumor suppressor genes in natural killer-cell malignancies. Leukemia. 2009; 23(6):1139-51. DOI: 10.1038/leu.2009.3. View

Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, Troxel A . Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest. 2003; 112(12):1809-20. PMC: 297002. DOI: 10.1172/JCI20039. View

Mizushima N, Yoshimori T, Ohsumi Y . The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol. 2011; 27:107-32. DOI: 10.1146/annurev-cellbio-092910-154005. View

Axe E, Walker S, Manifava M, Chandra P, Roderick H, Habermann A . Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J Cell Biol. 2008; 182(4):685-701. PMC: 2518708. DOI: 10.1083/jcb.200803137. View

Nishida Y, Arakawa S, Fujitani K, Yamaguchi H, Mizuta T, Kanaseki T . Discovery of Atg5/Atg7-independent alternative macroautophagy. Nature. 2009; 461(7264):654-8. DOI: 10.1038/nature08455. View

Nakatogawa H, Suzuki K, Kamada Y, Ohsumi Y . Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat Rev Mol Cell Biol. 2009; 10(7):458-67. DOI: 10.1038/nrm2708. View

Tsujimoto Y . Cell death regulation by the Bcl-2 protein family in the mitochondria. J Cell Physiol. 2003; 195(2):158-67. DOI: 10.1002/jcp.10254. View

LINDSTEN T, Ross A, King A, Zong W, Rathmell J, Shiels H . The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues. Mol Cell. 2001; 6(6):1389-99. PMC: 3057227. DOI: 10.1016/s1097-2765(00)00136-2. View

Clarke P . Developmental cell death: morphological diversity and multiple mechanisms. Anat Embryol (Berl). 1990; 181(3):195-213. DOI: 10.1007/BF00174615. View

10.

Kabeya Y, Kamada Y, Baba M, Takikawa H, Sasaki M, Ohsumi Y . Atg17 functions in cooperation with Atg1 and Atg13 in yeast autophagy. Mol Biol Cell. 2005; 16(5):2544-53. PMC: 1087256. DOI: 10.1091/mbc.e04-08-0669. View

11.

Baehrecke E . How death shapes life during development. Nat Rev Mol Cell Biol. 2002; 3(10):779-87. DOI: 10.1038/nrm931. View

12.

Shimizu S, Kanaseki T, Mizushima N, Mizuta T, Arakawa-Kobayashi S, Thompson C . Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol. 2004; 6(12):1221-8. DOI: 10.1038/ncb1192. View

13.

Huang X, Bai H, Chen L, Li B, Lu Y . Reduced expression of LC3B-II and Beclin 1 in glioblastoma multiforme indicates a down-regulated autophagic capacity that relates to the progression of astrocytic tumors. J Clin Neurosci. 2010; 17(12):1515-9. DOI: 10.1016/j.jocn.2010.03.051. View

14.

Wei M, Zong W, Cheng E, LINDSTEN T, Panoutsakopoulou V, Ross A . Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science. 2001; 292(5517):727-30. PMC: 3049805. DOI: 10.1126/science.1059108. View

15.

Yu L, Alva A, Su H, Dutt P, Freundt E, Welsh S . Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science. 2004; 304(5676):1500-2. DOI: 10.1126/science.1096645. View

16.

Shimizu S, Konishi A, Nishida Y, Mizuta T, Nishina H, Yamamoto A . Involvement of JNK in the regulation of autophagic cell death. Oncogene. 2010; 29(14):2070-82. DOI: 10.1038/onc.2009.487. View

17.

Kundu M, Lindsten T, Yang C, Wu J, Zhao F, Zhang J . Ulk1 plays a critical role in the autophagic clearance of mitochondria and ribosomes during reticulocyte maturation. Blood. 2008; 112(4):1493-502. PMC: 2515143. DOI: 10.1182/blood-2008-02-137398. View

18.

Takamura A, Komatsu M, Hara T, Sakamoto A, Kishi C, Waguri S . Autophagy-deficient mice develop multiple liver tumors. Genes Dev. 2011; 25(8):795-800. PMC: 3078705. DOI: 10.1101/gad.2016211. View

19.

Shen S, Kepp O, Kroemer G . The end of autophagic cell death?. Autophagy. 2011; 8(1):1-3. DOI: 10.4161/auto.8.1.16618. View

20.

Yue Z, Jin S, Yang C, Levine A, Heintz N . Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci U S A. 2003; 100(25):15077-82. PMC: 299911. DOI: 10.1073/pnas.2436255100. View