The Potential Role of Mitochondrial Acetaldehyde Dehydrogenase 2 in Urological Cancers From the Perspective of Ferroptosis and Cellular Senescence

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2022 May 6

PMID 35517510

Authors

Weizhen Zhu

Dechao Feng

Xu Shi

Qiang Wei

Lu Yang

Affiliations

Soon will be listed here.

Abstract

Overproduction of reactive oxygen species (ROS) and superlative lipid peroxidation promote tumorigenesis, and mitochondrial aldehyde dehydrogenase 2 (ALDH2) is associated with the detoxification of ROS-mediated lipid peroxidation-generated reactive aldehydes such as 4-hydroxy-2-nonenal (4-HNE), malondialdehyde, and acrolein due to tobacco smoking. ALDH2 has been demonstrated to be highly associated with the prognosis and chemoradiotherapy sensitivity of many types of cancer, including leukemia, lung cancer, head and neck cancer, esophageal cancer, hepatocellular cancer, pancreatic cancer, and ovarian cancer. In this study, we explored the possible relationship between ALDH2 and urological cancers from the aspects of ferroptosis, epigenetic alterations, proteostasis, mitochondrial dysfunction, and cellular senescence.

Citing Articles

Mechanisms and preventive measures of ALDH2 in ischemia‑reperfusion injury: Ferroptosis as a novel target (Review).

Han L, Zhai W Mol Med Rep. 2025; 31(4).

PMID: 40017132 PMC: 11876945. DOI: 10.3892/mmr.2025.13470.

[Activation of ALDH2 alleviates hypoxic pulmonary hypertension in mice by upregulating the SIRT1/PGC-1α signaling pathway].

Wang L, Bian F, Ma F, Fang S, Ling Z, Liu M Nan Fang Yi Ke Da Xue Xue Bao. 2024; 44(10):1955-1964.

PMID: 39523096 PMC: 11526457. DOI: 10.12122/j.issn.1673-4254.2024.10.14.

Molecular mechanisms of ferroptosis and its effects on bladder cancer.

Li R, Ning Y, Yuan Y, Yang X Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2024; 49(2):286-295.

PMID: 38755725 PMC: 11103069. DOI: 10.11817/j.issn.1672-7347.2024.230352.

Oxidative stress is two-sided in the treatment of acute myeloid leukemia.

Fan C, Yang X, Yan L, Shi Z Cancer Med. 2024; 13(9):e6806.

PMID: 38715546 PMC: 11077289. DOI: 10.1002/cam4.6806.

ALDH2 as an immunological and prognostic biomarker: Insights from pan-cancer analysis.

Shen X, Yan Z, Huang Y, Zhu Q, Zhang G, Ci H Medicine (Baltimore). 2024; 103(16):e37820.

PMID: 38640328 PMC: 11030019. DOI: 10.1097/MD.0000000000037820.

References

Shoeb M, Ansari N, Srivastava S, Ramana K . 4-Hydroxynonenal in the pathogenesis and progression of human diseases. Curr Med Chem. 2013; 21(2):230-7. PMC: 3964795. DOI: 10.2174/09298673113209990181. View

Litovkin K, Van Eynde A, Joniau S, Lerut E, Laenen A, Gevaert T . DNA Methylation-Guided Prediction of Clinical Failure in High-Risk Prostate Cancer. PLoS One. 2015; 10(6):e0130651. PMC: 4472347. DOI: 10.1371/journal.pone.0130651. View

Granados D, Tanguay P, Hardy M, Caron E, de Verteuil D, Meloche S . ER stress affects processing of MHC class I-associated peptides. BMC Immunol. 2009; 10:10. PMC: 2657905. DOI: 10.1186/1471-2172-10-10. View

Wu S, Chen J, Dong P, Zhang S, He Y, Sun L . Global gene expression profiling identifies ALDH2, CCNE1 and SMAD3 as potential prognostic markers in upper tract urothelial carcinoma. BMC Cancer. 2014; 14:836. PMC: 4242595. DOI: 10.1186/1471-2407-14-836. View

Miyasaka K, Kawanami T, Shimokata H, Ohta S, Funakoshi A . Inactive aldehyde dehydrogenase-2 increased the risk of pancreatic cancer among smokers in a Japanese male population. Pancreas. 2005; 30(2):95-8. DOI: 10.1097/01.mpa.0000147084.70125.41. View

Chen C, Sun L, Mochly-Rosen D . Mitochondrial aldehyde dehydrogenase and cardiac diseases. Cardiovasc Res. 2010; 88(1):51-7. PMC: 2936126. DOI: 10.1093/cvr/cvq192. View

Gu C, Xing Y, Jiang L, Chen M, Xu M, Yin Y . Impaired cardiac SIRT1 activity by carbonyl stress contributes to aging-related ischemic intolerance. PLoS One. 2013; 8(9):e74050. PMC: 3769351. DOI: 10.1371/journal.pone.0074050. View

Powers E, Morimoto R, Dillin A, Kelly J, Balch W . Biological and chemical approaches to diseases of proteostasis deficiency. Annu Rev Biochem. 2009; 78:959-91. DOI: 10.1146/annurev.biochem.052308.114844. View

Gorgoulis V, Adams P, Alimonti A, Bennett D, Bischof O, Bishop C . Cellular Senescence: Defining a Path Forward. Cell. 2019; 179(4):813-827. DOI: 10.1016/j.cell.2019.10.005. View

10.

Wang S, Wang L, Qin X, Turdi S, Sun D, Culver B . ALDH2 contributes to melatonin-induced protection against APP/PS1 mutation-prompted cardiac anomalies through cGAS-STING-TBK1-mediated regulation of mitophagy. Signal Transduct Target Ther. 2020; 5(1):119. PMC: 7378833. DOI: 10.1038/s41392-020-0171-5. View

11.

Fayet G, Jansson M, Sternberg D, Moslemi A, Blondy P, Lombes A . Ageing muscle: clonal expansions of mitochondrial DNA point mutations and deletions cause focal impairment of mitochondrial function. Neuromuscul Disord. 2002; 12(5):484-93. DOI: 10.1016/s0960-8966(01)00332-7. View

12.

Long P, He M, Yan W, Chen W, Wei D, Wang S . ALDH2 protects naturally aged mouse retina inhibiting oxidative stress-related apoptosis and enhancing unfolded protein response in endoplasmic reticulum. Aging (Albany NY). 2021; 13(2):2750-2767. PMC: 7880320. DOI: 10.18632/aging.202325. View

13.

van de Ven R, Santos D, Haigis M . Mitochondrial Sirtuins and Molecular Mechanisms of Aging. Trends Mol Med. 2017; 23(4):320-331. PMC: 5713479. DOI: 10.1016/j.molmed.2017.02.005. View

14.

Lopez-Otin C, Blasco M, Partridge L, Serrano M, Kroemer G . The hallmarks of aging. Cell. 2013; 153(6):1194-217. PMC: 3836174. DOI: 10.1016/j.cell.2013.05.039. View

15.

Singh K, Kulawiec M . Mitochondrial DNA polymorphism and risk of cancer. Methods Mol Biol. 2008; 471:291-303. PMC: 2825891. DOI: 10.1007/978-1-59745-416-2_15. View

16.

Wang Q, Williamson M, Bott S, Brookman-Amissah N, Freeman A, Nariculam J . Hypomethylation of WNT5A, CRIP1 and S100P in prostate cancer. Oncogene. 2007; 26(45):6560-5. DOI: 10.1038/sj.onc.1210472. View

17.

Tao Y, Huang X, Xie Y, Zhou X, He X, Tang S . Genome-wide association and gene-environment interaction study identifies variants in ALDH2 associated with serum ferritin in a Chinese population. Gene. 2018; 685:196-201. DOI: 10.1016/j.gene.2018.11.001. View

18.

Vatsyayan R, Chaudhary P, Sharma A, Sharma R, Lelsani P, Awasthi S . Role of 4-hydroxynonenal in epidermal growth factor receptor-mediated signaling in retinal pigment epithelial cells. Exp Eye Res. 2010; 92(2):147-54. PMC: 3064457. DOI: 10.1016/j.exer.2010.11.010. View

19.

Li R, Zhao Z, Sun M, Luo J, Xiao Y . ALDH2 gene polymorphism in different types of cancers and its clinical significance. Life Sci. 2016; 147:59-66. DOI: 10.1016/j.lfs.2016.01.028. View

20.

Ischia J, So A . The role of heat shock proteins in bladder cancer. Nat Rev Urol. 2013; 10(7):386-95. DOI: 10.1038/nrurol.2013.108. View