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Extracellular vesicles derived from Lactobacillus plantarum restore chemosensitivity through the PDK2-mediated glucose metabolic pathway in 5-FU-resistant colorectal cancer cells
JaeJin An , Eun-Mi Ha
J. Microbiol. 2022;60(7):735-745.   Published online July 4, 2022
DOI: https://doi.org/10.1007/s12275-022-2201-1
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  • 18 Web of Science
  • 16 Crossref
AbstractAbstract
Metabolic abnormalities are one of the main hallmarks of cancer and are associated with chemoresistance. Therefore, targeting the metabolic reprogramming of cancer cells has the potential to overcome chemoresistance. Probiotic-derived extracellular vesicles (EVs) play important roles in biological function and intracellular communication. However, the inhibitory effect of Lactobacillus plantarum-derived EVs (LpEVs) on colorectal cancer (CRC) cells has not yet been elucidated. This study clearly revealed that increased glycolysis in 5-fluorouracil (5-FU)-resistant CRC cells (CRC/5FUR) is directly related to chemoresistance and that the metabolic shift reversed by LpEVs inhibits cancer cell proliferation and eventually leads to apoptosis. Pyruvate dehydrogenase kinase 2 (PDK2), one of the crucial enzymes for enhancing glycolysis, was upregulated in CRC/5FUR cells. In our study, LpEVs sensitized CRC/5FUR cells to 5-FU by attenuating PDK2 expression in p53-p21-dependent metabolic signaling, thereby circumventing 5-FU resistance. We demonstrated the effect of cellular responses to 5-FU by modifying the PDK2 expression level in both 5-FU-sensitive parental CRC and 5- FU resistant CRC cell lines. Finally, we revealed that the PDK2 signaling pathway can potentially be targeted using LpEVs treatment to overcome chemoresistant CRC, thereby providing a potential strategy for CRC treatment by intervening in tumor metabolism.

Citations

Citations to this article as recorded by  
  • Effect of probiotic extracellular vesicles and their applications on health and disease
    Guangzhao Wang, Yang Wang, Kangliang Sheng, Yongzhong Wang
    Journal of the Science of Food and Agriculture.2025;[Epub]     CrossRef
  • Incorporation of recombinant proteins into extracellular vesicles by Lactococcus cremoris
    Tina Vida Plavec, Kristina Žagar Soderžnik, Giulia Della Pelle, Špela Zupančič, Robert Vidmar, Aleš Berlec
    Scientific Reports.2025;[Epub]     CrossRef
  • The benefits of Lactiplantibacillus plantarum: From immunomodulator to vaccine vector
    Joshua Tobias, Stefan Heinl, Kristina Dendinovic, Ajša Ramić, Anna Schmid, Catherine Daniel, Ursula Wiedermann
    Immunology Letters.2025; 272: 106971.     CrossRef
  • Interconnections within the tumor microenvironment: extracellular vesicles as critical players of metabolic reprogramming in tumor cells
    Carol Costa Encarnação, Giselle Marianne Faria, Victor Aguiar Franco, Luiz Gabriel Xavier Botelho, João Alfredo Moraes, Mariana Renovato-Martins
    Journal of Cancer Metastasis and Treatment.2024;[Epub]     CrossRef
  • Review of METTL3 in colorectal cancer: From mechanisms to the therapeutic potential
    Lexuan Zhang, Zhenwei Mao, Kai Yin, Shengjun Wang
    International Journal of Biological Macromolecules.2024; 277: 134212.     CrossRef
  • Extracellular Vesicles from Lacticaseibacillus Paracasei PC-H1 Inhibit HIF-1α-Mediated Glycolysis of Colon Cancer
    Yangqian Shi, Chunliang Zhang, Wanyu Cao, Luyi Li, Kaili Liu, Hanyue Zhu, Fikadu Balcha, Yong Fang
    Future Microbiology.2024; 19(3): 227.     CrossRef
  • Role of probiotic extracellular vesicles in inter-kingdom communication and current technical limitations in advancing their therapeutic utility
    Rahul Sanwlani, Kyle Bramich, Suresh Mathivanan
    Extracellular Vesicles and Circulating Nucleic Acids.2024; : 609.     CrossRef
  • Beneficial microbiome and diet interplay in early-onset colorectal cancer
    Zhengyuan Zhou, Linda Kleis, Ana Depetris-Chauvin, Stefanie Jaskulski, Victoria Damerell, Karin B Michels, Biljana Gigic, Ute Nöthlings, Gianni Panagiotou
    EMBO Molecular Medicine.2024; 17(1): 9.     CrossRef
  • Deciphering the role of host-gut microbiota crosstalk via diverse sources of extracellular vesicles in colorectal cancer
    Yun Song, Min Shi, Yugang Wang
    Molecular Medicine.2024;[Epub]     CrossRef
  • Targeting the gut and tumor microbiome in cancer treatment resistance
    Sona Ciernikova, Aneta Sevcikova, Michal Mego
    American Journal of Physiology-Cell Physiology.2024; 327(6): C1433.     CrossRef
  • Lactobacillus plantarum Metabolites Elicit Anticancer Effects by Inhibiting Autophagy-Related Responses
    Sihyun Jeong, Yuju Kim, Soyeong Park, Doyeon Lee, Juho Lee, Shwe Phyu Hlaing, Jin-Wook Yoo, Sang Hoon Rhee, Eunok Im
    Molecules.2023; 28(4): 1890.     CrossRef
  • Extracellular Vesicles of Probiotics: Shedding Light on the Biological Activity and Future Applications
    Paweł Krzyżek, Beatrice Marinacci, Irene Vitale, Rossella Grande
    Pharmaceutics.2023; 15(2): 522.     CrossRef
  • Isolation and Characterization of Cow-, Buffalo-, Sheep- and Goat-Milk-Derived Extracellular Vesicles
    Monisha Samuel, Rahul Sanwlani, Mohashin Pathan, Sushma Anand, Ella L. Johnston, Ching-Seng Ang, Maria Kaparakis-Liaskos, Suresh Mathivanan
    Cells.2023; 12(20): 2491.     CrossRef
  • Gut microbiota in colorectal cancer development and therapy
    Chi Chun Wong, Jun Yu
    Nature Reviews Clinical Oncology.2023; 20(7): 429.     CrossRef
  • Phytochemicals targeting glycolysis in colorectal cancer therapy: effects and mechanisms of action
    Lu Zhan, Fangting Su, Qiang Li, Yueqiang Wen, Feng Wei, Zhelin He, Xiaoyan Chen, Xiang Yin, Jian Wang, Yilin Cai, Yuxia Gong, Yu Chen, Xiao Ma, Jinhao Zeng
    Frontiers in Pharmacology.2023;[Epub]     CrossRef
  • Crosstalk between gut microbiota and RNA N6-methyladenosine modification in cancer
    Hao Su, Henley Cheung, Harry Cheuk-Hay Lau, Hongyan Chen, Xiaoting Zhang, Na Qin, Yifei Wang, Matthew Tak Vai Chan, William Ka Kei Wu, Huarong Chen
    FEMS Microbiology Reviews.2023;[Epub]     CrossRef
Geographic diversity in Helicobacter pylori oipA genotype between Korean and United States isolates
Aeryun Kim , Jing Lai , D. Scott Merrell , Ji-Hye Kim , Hanfu Su , Jeong-Heon Cha
J. Microbiol. 2021;59(12):1125-1132.   Published online October 31, 2021
DOI: https://doi.org/10.1007/s12275-021-1450-8
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  • 4 Web of Science
  • 2 Crossref
AbstractAbstract
Helicobacter pylori outer membrane inflammatory protein A (OipA) was originally named for its role in inducing inflammation in the host, as evidenced by high mucosal IL-8 levels. Expression of OipA is regulated by phase variation of a CT dinucleotide-repeat located in the 5􍿁􀁇region of the gene. However, little is known about OipA geographic diversity across isolates. To address this gap, we conducted a large-scale molecular epidemiologic analysis using H. pylori clinical isolates obtained from two geographically distinct populations: Korea and the United States (US). Most Korean isolates (98.7%) possessed two copies of oipA located at two specific loci (A and B) while all US isolates contained only one copy of oipA at locus A. Furthermore, most Korean oipA (94.8%) possessed three or less CT repeats while most US oipA (96.6%) contained five or more CT repeats. Among the two copies, all Korean H. pylori possessed at least one oipA ‘on’ phase variant while the single copy of oipA in US isolates showed 56.2% ‘on’ and 43.8% ‘off.’ Thus, host differences seem to have driven geographic diversification of H. pylori across these populations such that OipA expression in US isolates is still regulated by phase variation with 5 or more CT repeats, while Korean isolates always express OipA; duplication of the oipA combined with a reduction of CT repeats to three or less ensures continued expression. En masse, these findings suggest that diversity in the oipA gene copy number, CT repeats, and phase variation among H. pylori from different populations may confer a benefit in adaptation to particular host populations.

Citations

Citations to this article as recorded by  
  • Genetic diversity of the oipA gene among Helicobacter pylori isolates and clinical outcome in Vietnam
    Thi Hong Nhung Thai, Hong Phong Nguyen, Thi Hai Yen Nguyen, Thi Be Hai Nguyen, Thai Hoa Nguyen, Thi Mai Ngan Nguyen, Thi Minh Thi Ha
    Infection, Genetics and Evolution.2023; 112: 105438.     CrossRef
  • Characterization of East-Asian Helicobacter pylori encoding Western EPIYA-ABC CagA
    Kavinda Tissera, Myeong-A Kim, Jing Lai, Sacheera Angulmaduwa, Aeryun Kim, D. Scott Merrell, Ji-Hye Kim, Hanfu Su, Jeong-Heon Cha
    Journal of Microbiology.2022; 60(2): 207.     CrossRef

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