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dc.contributor.authorTykhomyrov, A.A. and Nedzvetsky, V.S. and Aĝca, C.A. and Guzyk, M.M. and Korsa, V.V. and Grinenko, T.V.
dc.date.accessioned2021-04-08T12:06:05Z
dc.date.available2021-04-08T12:06:05Z
dc.date.issued2020
dc.identifier10.32471/exp-oncology.2312-8852.vol-42-no-4.15253
dc.identifier.issn18129269
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85099077698&doi=10.32471%2fexp-oncology.2312-8852.vol-42-no-4.15253&partnerID=40&md5=1d810a9d99ded53f4555e6433f53a803
dc.identifier.urihttp://acikerisim.bingol.edu.tr/handle/20.500.12898/3836
dc.description.abstractPericellular plasmin generation triggers apoptosis/anoikis in normal adherent cells. However, cancer cells are notoriously resistant to anoikis, enabling metastasis and new tumor growth beyond their original environment. Autophagy can be a major contributor to anoikis resistance in cancer. Aim: To investigate if protective autophagy can be induced in lung adenocarcinoma cells in response to plasminogen treatment. Materials and Methods: Human lung adenocarcinoma A549 cells were incubated with Glu-plasminogen (0.1-1.0 µM) for 24 h. Pericellular plasmin activity was monitored spectrophotometrically by a cleavage of the specific chromogenic substrate S-2251. Cell survival was assessed by 3-[4,5-dimethyl thiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT)-test. Degradation of fibronectin, levels of autophagy markers (beclin-1 and light chain 3 (LC3)) and glycolysis regulator (TIGAR) were evaluated by western blot. Intracellular localization of LC-3 was visualized by immunocytochemistry. Results: It was shown that plasminogen is converted into plasmin on the surface of adenocarcinoma cells in a dose-dependent manner. Plasmin disrupted cellular adhesive contacts resulting in cell detachment. A549 cells did not loss their viability after plasminogen treatment for 24 h, while 1.0 µM plasminogen was cytotoxic for non-transformed fibroblasts. Plasminogen 0.1, 0.5, and 1.0 µM induced 7.08-, 5.18-, and 3.78-fold elevation of TIGAR expression (p < 0.05), respectively. Enhanced TIGAR expression indicates switch on pentose phosphate pathway, protection against oxidative stress to prevent apoptosis, facilitation of DNA repair and the degradation of their own organelles (autophagy). Exposure of adenocarcinoma cells to plasminogen in concentrations of 0.1 and 0.5 µM caused 1.74- and 2.19-fold elevation of beclin-1 expression vs untreated cells (p < 0.05), respectively. Unlike K1-3 fragment, plasminogen treatment (0.1-0.5 µM) resulted in increased expression of LC3-I and stimulated rapid conversion of LC3-I to LC3-II. Up-regulation of beclin-1 levels and enhanced LC3-I/II conversion in plasminogen-treated A549 cells are the hallmarks of autophagy induction. According to immunocytochemistry data, increased LC3 puncta and autophagosome formation after exposure to plasminogen could reflect autophagy activation. Conclusions: Therefore, we showed stimulation of prosurvival signals and induction of autophagy in plasminogen-treated adenocarcinoma cells rendering them resistant to apoptosis/anoikis. Based on the obtained data, autophagy has a great potential for novel targets that affect cancer cell death, in addition to the current cytotoxic agents. © Experimental Oncology, 2020
dc.language.isoEnglish
dc.sourceExperimental Oncology
dc.titlePlasminogen/plasmin affects expression of glycolysis regulator tigar and induces autophagy in lung adenocarcinoma a549 cells


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