Caenorhabditis elegans as a Valuable Model for Studying Apoptosis and Autophagy in Cancer Development: Current insights, Future directions, and Challenges
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Abstract
Despite significant progress in the fight against cancer, cancer treatment remains a significant public health concern and a societal burden worldwide. To develop better intervention strategies to counter tumor development, it is important to understand the molecular and cellular mechanisms underlying oncogenic diseases. In-vivo and in-vitro models have traditionally been utilized to understand the biological processes involved in cancer, including apoptosis, proliferation, angiogenesis, invasion, metastasis, genome instability, and metabolism. The present review aims to look at the way Caenorhabditis elegans (C. elegans) can affect cancer cellular and molecular bases, concentrating on mechanisms like apoptosis and autophagy. In recent years, . elegans has emerged as a promising model organism for studying the molecular basis of tumorigenesis. This model organism is attractive since it is genetically tractable and has a simple and well-understood anatomy. The C. elegans exhibits conserved cellular pathways and mechanisms relevant to human diseases, including cancer. Furthermore, C. elegans has been used to study the roles of tumor suppressor genes and oncogenes in tumorigenesis. In conclusion, C. elegans is an emerging animal model that has the potential to facilitate the development of better intervention strategies to prevent or counter tumor development and to advance our understanding of cancer progression with further research.
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References
Li Y, Zhong L, Zhang L, Shen X, Kong L, and Wu T. Research advances on the adverse effects of nanomaterials in a model organism, Caenorhabditis elegans. Environ Toxicol Chem. 2021; 40(9): 2406-2424. DOI: https://doi.org/10.1002/etc.5133
Leung MC, Williams PL, Benedetto A, Au C, Helmcke KJ, Aschner M, et al. Caenorhabditis elegans: an emerging model in biomedical and environmental toxicology. Toxicol Sci. 2008; 106(1): 5-28. DOI: https://doi.org/10.1093/toxsci/kfn121
Gruber J, Chen CB, Fong S, Ng LF, Teo E, and Halliwell B. Caenorhabditis elegans: what we can and cannot learn from aging worms. Antioxid Redox Signal. 2015; 23(3): 256-279. DOI: https://doi.org/10.1089/ars.2014.6210
Corsi AK, Wightman B, and Chalfie M. A transparent window into biology: a primer on Caenorhabditis elegans. Genetics. 2015; 200(2): 387-407. DOI: https://doi.org/10.1534/genetics.115.176099
Kyriakakis E, Markaki M, and Tavernarakis N. Caenorhabditis elegans as a model for cancer research. Mol Cell Oncol. 2015; 2(2): e975027. DOI: https://doi.org/10.4161/23723556.2014.975027
Kaletta T, and Hengartner MO. Finding function in novel targets: C. elegans as a model organism. Nat Rev Drug Discov. 2006; 5(5): 387-399. DOI: https://doi.org/10.1038/nrd2031
Markaki M and Tavernarakis N. Caenorhabditis elegans as a model system for human diseases. Curr Opin Biotechnol. 2020; 63: 118-125. DOI: https://doi.org/10.1016/j.copbio.2019.12.011
Hanahan D, and Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144(5): 646-674. DOI: https://doi.org/10.1016/j.cell.2011.02.013
Jiramongkol Y, and Lam EW-F. FOXO transcription factor family in cancer and metastasis. Cancer Metastasis Rev. 2020; 39:681-709. DOI: https://doi.org/10.1007/s10555-020-09883-w
Honnen S. Caenorhabditis elegans as a powerful alternative model organism to promote research in genetic toxicology and biomedicine. Arch Toxicol. 2017; 91(5): 2029-2044. DOI: https://doi.org/10.1007/s00204-017-1944-7
Steele LM, Kotsch TJ, Legge CA, and Smith DJ. Establishing C. elegans as a Model for Studying the Bioeffects of Therapeutic Ultrasound. Ultrasound Med Biol. 2021; 47(8): 2346-2359. DOI: https://doi.org/10.1016/j.ultrasmedbio.2021.04.005
Rothman J, and Jarriault S. Developmental plasticity and cellular reprogramming in caenorhabditis elegans. Genetics. 2019; 213(3): 723-757. DOI: https://doi.org/10.1534/genetics.119.302333
Hulme SE, and Whitesides GM. Chemistry and the worm: Caenorhabditis elegans as a platform for integrating chemical and biological research. Angewandte Chemie Int Edition. 2011; 50(21): 4774-4807. DOI: https://doi.org/10.1002/anie.201005461
Nigon VM, and Félix MA. History of research on C. elegans and other free-living nematodes as model organisms. WormBook: The Online Review of C elegans Biol. 2018.
Cornaglia M, Lehnert T, and Gijs MA. Microfluidic systems for high-throughput and high-content screening using the nematode Caenorhabditis elegans. Lab Chip. 2017; 17(22): 3736-3759. DOI: https://doi.org/10.1039/C7LC00509A
Zhang S, Li F, Zhou T, Wang G, and Li Z. Caenorhabditis elegans as a useful model for studying aging mutations. Front Endocrinol. 2020; 11: 554994. DOI: https://doi.org/10.3389/fendo.2020.554994
Gonzalez-Moragas L, Roig A, and Laromaine A. C. elegans as a tool for in vivo nanoparticle assessment. Adv Colloid Interface Sci. 2015; 219: 10-26. DOI: https://doi.org/10.1016/j.cis.2015.02.001
Ganner A, and Neumann-Haefelin E. Genetic kidney diseases: Caenorhabditis elegans as model system. Cell Tiss Res. 2017; 369: 105-118. DOI: https://doi.org/10.1007/s00441-017-2622-z
Zhu A, Zheng F, Zhang W, Li L, Li Y, Hu H, et al. Oxidation and antioxidation of natural products in the model organism Caenorhabditis elegans. Antioxidants. 2022; 11(4): 705. DOI: https://doi.org/10.3390/antiox11040705
Giunti S, Andersen N, Rayes D, and De Rosa MJ. Drug discovery: Insights from the invertebrate Caenorhabditis elegans. Pharmacol Res Perspect. 2021; 9(2): e00721. DOI: https://doi.org/10.1002/prp2.721
Przybyla L, and Gilbert LA. A new era in functional genomics screens. Nat Rev Genet. 2022; 23(2): 89-103. DOI: https://doi.org/10.1038/s41576-021-00409-w
Liu L, Li H, Hu D, Wang Y, Shao W, Zhong J, et al. Insights into N6-methyladenosine and programmed cell death in cancer. Mol Cancer. 2022; 21(1): 1-16. DOI: https://doi.org/10.1186/s12943-022-01508-w
Martínez-Reyes I, and Chandel NS. Cancer metabolism: looking forward. Nat Rev Cancer. 2021; 21(10): 669-680. DOI: https://doi.org/10.1038/s41568-021-00378-6
Hunt PR, Camacho JA, and Sprando RL. Caenorhabditis elegans for predictive toxicology. Curr Opin Toxicol. 2020; 23: 23-28. DOI: https://doi.org/10.1016/j.cotox.2020.02.004
Dall KB, and Færgeman NJ. Metabolic regulation of lifespan from a C. elegans perspective. Genes Nutr. 2019; 14(1): 1-12. DOI: https://doi.org/10.1186/s12263-019-0650-x
Auger C, Vinaik R, Appanna VD, and Jeschke MG. Beyond mitochondria: Alternative energy-producing pathways from all
strata of life. Metabolism. 2021; 118: 154733. DOI: https://doi.org/10.1016/j.metabol.2021.154733
Kumar A, Baruah A, Tomioka M, Iino Y, Kalita MC, and Khan M. Caenorhabditis elegans: a model to understand host-microbe interactions. Cell Mol Life Sci. 2020;77: 1229-1249. DOI: https://doi.org/10.1007/s00018-019-03319-7
García-González AP, Ritter AD, Shrestha S, Andersen EC, Yilmaz LS, and Walhout AJ. Bacterial metabolism affects the C. elegans response to cancer chemotherapeutics. Cell. 2017; 169(3): 431-441. e8. DOI: https://doi.org/10.1016/j.cell.2017.03.046
Ajani JA, Song S, Hochster HS, and Steinberg IB. Cancer stem cells: the promise and the potential. Semin Oncol; 2015: Elsevier. DOI: https://doi.org/10.1053/j.seminoncol.2015.01.001
Kagoshima H, Shigesada K, and Kohara Y. RUNX regulates stem cell proliferation and differentiation: insights from studies of C. elegans. J cell biochem. 2007; 100(5): 1119-1130. DOI: https://doi.org/10.1002/jcb.21174
Hansen D, and Schedl T. Stem cell proliferation versus meiotic fate decision in Caenorhabditis elegans. Germ Cell Development in C elegans. 2013: 71-99. DOI: https://doi.org/10.1007/978-1-4614-4015-4_4
Wang YA, Kammenga JE, and Harvey SC. Genetic variation in neurodegenerative diseases and its accessibility in the model organism Caenorhabditis elegans. Hum Genomics. 2017; 11(1):1-10. DOI: https://doi.org/10.1186/s40246-017-0108-4
Wong SQ, Kumar AV, Mills J, and Lapierre LR. C. elegans to model autophagy-related human disorders. Prog Mol Biol Transl Sci. 2020; 172: 325-373. DOI: https://doi.org/10.1016/bs.pmbts.2020.01.007
Shirjang S, Mansoori B, Asghari S, Duijf PH, Mohammadi A, Gjerstorff M, et al. MicroRNAs in cancer cell death pathways: Apoptosis
and necroptosis. Free Radic. 2019; 139: 1-15. DOI: https://doi.org/10.1016/j.freeradbiomed.2019.05.017
Sahebi R, Akbari N, Bayat Z, Rashidmayvan M, Mansoori A, Beihaghi M. A Summary of Autophagy Mechanisms in Cancer Cells. Research in Biotechnology and Environmental Science. 2022; 1(1): 28-35. https://rbes.rovedar.com/article_160846.html
Bommer GT, Gerin I, Feng Y, Kaczorowski AJ, Kuick R, Love RE, et al. p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr biol. 2007; 17(15): 1298-1307. DOI: https://doi.org/10.1016/j.cub.2007.06.068
Raju D, Hussey S, Ang M, Terebiznik MR, Sibony M, Galindo-Mata E, et al. Vacuolating cytotoxin and variants in Atg16L1 that disrupt autophagy promote Helicobacter pylori infection in humans. Gastroenterology. 2012; 142(5): 1160-1171. DOI: https://doi.org/10.1053/j.gastro.2012.01.043
Kobet RA, Pan X, Zhang B, Pak SC, Asch AS, and Lee M-H. Caenorhabditis elegans: A model system for anti-cancer drug discovery and therapeutic target identification. Biomol Ther. 2014; 22(5): 371. DOI: https://doi.org/10.4062/biomolther.2014.084
Artal‐Sanz M, de Jong L, and Tavernarakis N. Caenorhabditis elegans: a versatile platform for drug discovery. J Health Care Technol. 2006; 1(12): 1405-1418. DOI: https://doi.org/10.1002/biot.200600176
Leung RK, and Whittaker PA. RNA interference: from gene silencing to gene-specific therapeutics. Pharmacol Ther. 2005; 107(2): 222-239. DOI: https://doi.org/10.1016/j.pharmthera.2005.03.004
Iorns E, Lord CJ, Turner N, and Ashworth A. Utilizing RNA interference to enhance cancer drug discovery. Nat Rev Drug Discov. 2007; 6(7): 556-568. DOI: https://doi.org/10.1038/nrd2355
Hannon GJ, and Rossi JJ. Unlocking the potential of the human genome with RNA interference. Nature. 2004; 431(7006): 371-378. DOI: https://doi.org/10.1038/nature02870
Hesp K, Smant G, and Kammenga JE. Caenorhabditis elegans DAF-16/FOXO transcription factor and its mammalian homologs associate with age-related disease. Exp Gerontol. 2015; 72: 1-7. DOI: https://doi.org/10.1016/j.exger.2015.09.006
Li Z, Pearlman AH, and Hsieh P. DNA mismatch repair and the DNA damage response. DNA repair. 2016; 38: 94-101. DOI: https://doi.org/10.1016/j.dnarep.2015.11.019
Abuetabh Y, Wu HH, Chai C, Al Yousef H, Persad S, Sergi CM, et al. DNA damage response revisited: the p53 family and its regulators provide endless cancer therapy opportunities. Exp Mol Med. 2022; 54(10): 1658-1669. DOI: https://doi.org/10.1038/s12276-022-00863-4
Schumacher B, Hanazawa M, Lee MH, Nayak S, Volkmann K, Hofmann R, et al. Translational repression of C. elegans p53 by GLD-1 regulates DNA damage-induced apoptosis. Cell. 2005; 120(3): 357-368.
DOI: 10.1016/j.cell.2004.12.009
Jolliffe AK, and Derry WB. The TP53 signaling network in mammals and worms. Brief Funct Genomics. 2013; 12(2): 129-141. DOI: https://doi.org/10.1093/bfgp/els047
Murphy CT, and Hu PJ. Insulin/insulin-like growth factor signaling in C. elegans. WormBook: The Online Review of C elegans Biology. 2018.
Wang H, Liu H, Chen K, Xiao J, He K, Zhang J, et al. SIRT1 promotes tumorigenesis of hepatocellular carcinoma through PI3K/PTEN/AKT signaling. Oncol rep. 2012; 28(1): 311-8.
Cui M, Cohen ML, Teng C, and Han M. The tumor suppressor Rb critically regulates starvation-induced stress response in C. elegans. Curr Bio. 2013; 23(11): 975-980. DOI: https://doi.org/10.1016/j.cub.2013.04.046
Liu J, and Chin-Sang ID. C. elegans as a model to study PTEN's regulation and function. Methods. 2015; 77: 180-190. DOI: https://doi.org/10.1016/j.ymeth.2014.12.009
Kipreos ET, and van den Heuvel S. Developmental control of the cell cycle: insights from Caenorhabditis elegans. Genetics. 2019; 211(3): 797-829. DOI: https://doi.org/10.1534/genetics.118.301643
Mizumoto K, and Sawa H. Cortical β-catenin and APC regulate asymmetric nuclear β-catenin localization during asymmetric cell division in C. elegans. Dev Cell. 2007; 12(2): 287-299. DOI: https://doi.org/10.1016/j.devcel.2007.01.004
Kirienko NV, Mani K, and Fay DS. Cancer models in Caenorhabditis elegans. Dev Dyn DEV DYNAM. 2010; 239(5): 1413-1448. DOI: https://doi.org/10.1002/dvdy.22247
Rodriguez M, Snoek LB, De Bono M, and Kammenga JE. Worms under stress: C. elegans stress response and its relevance to complex human disease and aging. Trends Genet. 2013; 29(6): 367-374. DOI: https://doi.org/10.1016/j.tig.2013.01.010
Denton D, Nicolson S, and Kumar S. Cell death by autophagy: facts and apparent artefacts. Cell Death Differ. 2012; 19(1): 87-95. DOI: https://doi.org/10.1038/cdd.2011.146
Markaki M, and Tavernarakis N. Modeling human diseases in Caenorhabditis elegans. Biotechnol J. 2010; 5(12): 1261-1276. DOI: https://doi.org/10.1002/biot.201000183
Yarychkivska O, Sharmin R, Elkhalil A, Ghose P, editors. Apoptosis and beyond: A new era for programmed cell death in Caenorhabditis elegans. Semin Cell Dev. 2023: Elsevier. DOI: https://doi.org/10.1016/j.semcdb.2023.02.003
Hastie E, Sellers R, Valan B, Sherwood DR. A scalable CURE using A CRISPR/Cas9 fluorescent protein knock-in strategy in Caenorhabditis elegans. J microbiol biol educ. 2019; 20(3): 70. DOI: https://doi.org/10.1128/jmbe.v20i3.1847
Dow LE. Modeling disease in vivo with CRISPR/Cas9. Trends Mol Med. 2015; 21(10): 609-621. DOI: https://doi.org/10.1016/j.molmed.2015.07.006