3rd International Conference on Chemo and BioInformatics, Kragujevac, September 25-26. 2025. (pp. 327-330)
АУТОР(И) / AUTHOR(S): Halime Akgun, Oguzhan Akgun, Enes Mehmet Serbetci, Didem Akyoney, Elif Erturk, Digdem Yoyen-Ermis, Haluk Barbaros Oral, Ferda Ari
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DOI: 10.46793/ICCBIKG25.327A
САЖЕТАК / ABSTRACT:
Therapy resistance and metastatic relapse remain major barriers to effective lung cancer treatment. Emerging evidence suggests that anastasis—the reversal of apoptosis—may allow cancer cells to survive cytotoxic stress and acquire more aggressive phenotypes. However, whether anastasis systematically engages epithelial-to-mesenchymal transition (EMT) programs and which signaling networks are conserved across models remain largely unexplored.
Here, we combined mechanistic in vitro studies with integrated multi-cohort transcriptomic analyses to define the molecular landscape of EMT following anastasis. In A549 lung adenocarcinoma cells, paclitaxel-induced apoptosis was reversed by stimulus withdrawal, and recovering cells were isolated by flow cytometry based on Annexin V and Caspase-3/7 activity. During recovery, apoptotic signatures diminished while EMT drivers (E-cadherin↓, Vimentin↑, Snail↑, Slug↑) were robustly induced, accompanied by a marked increase in cell migration and invasion. By integrating mRNA- and protein-level validation with cross-platform transcriptomic profiling, we generated a multi-layered molecular view of EMT during anastasis.
To determine whether these features represent a conserved program, we re-analyzed RNA-seq and microarray datasets from diverse cancer models. Meta-analysis and enrichment profiling consistently identified EMT activation alongside TGF-β, MAPK, HIF-1, and NF-κB signaling pathways during anastasis. Single-sample GSEA confirmed a strong correlation between EMT and an “Anastasis-Core” gene signature across datasets, paralleling our experimental observations.
These findings define a conserved EMT-driven molecular program engaged during anastasis, highlighting post-apoptotic plasticity as a therapeutic vulnerability that could be exploited to block therapy resistance and metastatic relapse in lung cancer.
КЉУЧНЕ РЕЧИ / KEYWORDS:
anastasis, epithelial-to-mesenchymal transition (EMT), lung adenocarcinoma, apoptosis, transcriptomic profiling
ПРОЈЕКАТ / ACKNOWLEDGEMENT:
This research was supported by the Scientific and Technological Research Council of Türkiye (TÜBİTAK, 1001 Project No. 123Z073). We thank Bursa Uludag Molecular Cancer Research Laboratory (BUMKAL) for their valuable support and contributions to this study.
ЛИТЕРАТУРА / REFERENCES:
- R. L. Sıegel, K.D. Mıller, N.S. Wagle, A. Jemal., Cancer Statistics, 2024, Ca: A Cancer Journal For Clinicians, 74 (2024) 7–33. https://doi.org/10.3322/Caac.21823.
- S. Elmore., Apoptosis: A Review Of Programmed Cell Death, Toxicologic Pathology, 35 (2007) 495–516. https://doi.org/10.1080/01926230701320337.
- H. L. Tang, H.M. Tang, K.H. Mak, S. Hu, S.S. Wang, K.M. Wong, C.S. Wong, H.Y. Wu, H.T. Law, K. Lıu, C.C. Talbot Jr, W.K. Lau, D.J. Montell, M.C. Fung., Cell Survival, Dna Damage, and Oncogenic Transformation After A Transient and Reversible Apoptotic Response, Molecular Biology Of The Cell, 23 (2012) 2240–2252. https://doi.org/10.1091/Mbc.E11-11-0926.
- J. Dudas, A. Ladanyı, J. Ingruber, T.B. Steınbıchler, H. Rıechelmann., Epithelial To Mesenchymal Transition: A Mechanism That Fuels Cancer Radio/Chemoresistance, Cells, 9 (2020) 428. https://doi.org/10.3390/Cells9020428.
- H. M. Tang, H.L. Tang., Unravelling The Pathological Roles Of Anastasis in Cancer Recurrence, Open Biology, 15 (2025) 240270. http://doi.org/10.1098/Rsob.240270.
- T. L. Weıgel, M.T. Lotze, P.K. Kım, A.A. Amoscato, J.D. Luketıch, C. Odoux., Paclitaxel-Induced Apoptosis in Non–Small Cell Lung Cancer Cell Lines is Associated With İncreased Caspase-3 Activity, The Journal Of Thoracic And Cardiovascular Surgery, 119 (2000) 795–803.
- H. M. Tang, H.L. Tang., Anastasis: Recovery From The Brink Of Cell Death, Royal Society Open Science, 5 (2018) 180442. https://doi.org/10.1098/Rsos.180442.
- M. Kanehısa, Y. Sato, M. Kawashıma, M. Furumıchı, M. Tanabe., Kegg as a Reference Resource for Gene and Protein Annotation, Nucleic Acids Research, 44 (2016) D457–D462. https://doi.org/10.1093/Nar/Gkv1070.
- K. Rothfels, M. Mılacıc, L. Matthews, R. Haw, C. Sevılla, M. Gıllespıe, R. Stephan, Gong, E. Ragueneau, B. May, V. Shamovsky, A. Wrıght, J. Weıser, D. Beavers, Conley, K. Tıwarı, B. Jassal, J. Grıss, A. Senff-Rıbeıro, T. Brunson, … L. Steın., Using The Reactome Database, Current Protocols, 3 (2023) E722. https://doi.org/10.1002/Cpz1.722.
- D. Szklarczyk, R. Kırsch, M. Koutroulı, K. Nastou, F. Mehryary, R. Hachılıf, A.L. Gable, T. Fang, N.T. Doncheva, S. Pyyasalo, P. Bork, L.J. Jensen, C. Von Merıng., The Strıng Database in 2023: Protein-Protein Association Networks and Functional Enrichment Analyses for Any Sequenced Genome of Interest, Nucleic Acids Research, 51 (2023) D638–D646. https://doi.org/10.1093/Nar/Gkac1000.
- M. Zhao, L. Kong, Y. Lıu, Et Al., Dbemt: An Epithelial-Mesenchymal Transition Associated Gene Resource, Scientific Reports, 5 (2015) 11459. https://doi.org/10.1038/Srep11459.
- S. V. Vasaıkar, A.P. Deshmukh, P. Den Hollander, S. Addankı, N.A. Kuburıch, S. Kudaravallı, R. Joseph, J.T. Chang, R. Soundararajan, S.A. Manı., Emtome: A Resource for Pan-Cancer Analysis of Epithelial-Mesenchymal Transition Genes and Signatures, British Journal Of Cancer, 124 (2021) 259–269. https://doi.org/10.1038/S41416-020-01178-9.
- K. Benoıt, K. Wıessenbach, Et Al., Quanteda: An R Package for the Quantitative Analysis of Textual Data, Journal Of Open Source Software, 3 (2018) 774. https://doi.org/10.21105/Joss.00774.
- P. Langfelder, S. Horvath., Wgcna: An R Package for Weighted Correlation Network Analysis, Bmc Bioinformatics, 9 (2008) 559. https://doi.org/10.1186/1471-2105-9-559.
- G. Yu, Et Al., Clusterprofiler: An R Package for Comparing Biological Themes Among Gene Clusters, Omıcs, 16 (2012) 284–287.