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000302294 1001_ $$00000-0003-0875-642X$$aChen, Oleg$$b0
000302294 245__ $$aAdaptation to Arginine Deprivation Leads to a More Aggressive, Therapy-Resistant Phenotype in HNSCC Cells.
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000302294 520__ $$aPurpose: The development of acquired resistance to arginine deprivation therapy (ADT) is a major barrier to its efficacy. This study aimed to elucidate the possible mechanisms underlying the resistance to ADT. Methods: We applied repeated ADT and established a subline SAS-R9 of the human head and neck squamous cell carcinoma (HNSCC) cells semi-resistant to arginine (Arg) deprivation in vitro. This subline was compared to the parental SAS cell lines for its relative clonogenic proliferation, aggregation, adhesion, and migration capacities. The transcriptomic changes were assessed by RNA sequencing. Signaling pathway alterations were confirmed by RT-PCR and Western blotting. Relative cell radioresistance was analyzed by radiobiological clonogenic survival assay. DNA double-strand break (DSB) repair was assessed by γH2A.X foci analysis. Results: SAS-R9 cells showed higher survival in response to ADT and radiotherapy, elevated clonogenic proliferation rate, cell-cell aggregation, and cell-matrix adhesion, along with increased epithelial-mesenchymal transition (EMT) markers and enhanced DNA DSB repair, potentially related to a more aggressive and therapy-resistant phenotype. Conclusions: While acute ADT has radiosensitizing potential, this new study suggests that long-term, repeated ADT is associated with cell selection and reprogramming, resulting in resistance to radiotherapy-induced DNA damage and higher tumor cell aggressiveness.
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000302294 650_7 $$2Other$$aDNA repair
000302294 650_7 $$2Other$$aacquired drug resistance
000302294 650_7 $$2Other$$aarginine deprivation therapy
000302294 650_7 $$2Other$$aepithelial–mesenchymal transition
000302294 650_7 $$2Other$$ahead and neck squamous cell carcinoma
000302294 650_7 $$2Other$$aradiosensitization
000302294 650_7 $$2Other$$arecombinant human arginase type 1
000302294 650_7 $$094ZLA3W45F$$2NLM Chemicals$$aArginine
000302294 650_2 $$2MeSH$$aHumans
000302294 650_2 $$2MeSH$$aArginine: deficiency
000302294 650_2 $$2MeSH$$aArginine: metabolism
000302294 650_2 $$2MeSH$$aSquamous Cell Carcinoma of Head and Neck: metabolism
000302294 650_2 $$2MeSH$$aSquamous Cell Carcinoma of Head and Neck: pathology
000302294 650_2 $$2MeSH$$aSquamous Cell Carcinoma of Head and Neck: genetics
000302294 650_2 $$2MeSH$$aCell Line, Tumor
000302294 650_2 $$2MeSH$$aHead and Neck Neoplasms: metabolism
000302294 650_2 $$2MeSH$$aHead and Neck Neoplasms: pathology
000302294 650_2 $$2MeSH$$aHead and Neck Neoplasms: genetics
000302294 650_2 $$2MeSH$$aEpithelial-Mesenchymal Transition: drug effects
000302294 650_2 $$2MeSH$$aCell Proliferation: drug effects
000302294 650_2 $$2MeSH$$aRadiation Tolerance
000302294 650_2 $$2MeSH$$aPhenotype
000302294 650_2 $$2MeSH$$aDrug Resistance, Neoplasm
000302294 650_2 $$2MeSH$$aCell Movement
000302294 650_2 $$2MeSH$$aDNA Repair
000302294 650_2 $$2MeSH$$aGene Expression Regulation, Neoplastic
000302294 650_2 $$2MeSH$$aDNA Breaks, Double-Stranded
000302294 650_2 $$2MeSH$$aCell Adhesion
000302294 650_2 $$2MeSH$$aCell Survival: drug effects
000302294 7001_ $$00000-0001-6703-457X$$aVovk, Olena$$b1
000302294 7001_ $$00009-0007-2915-4117$$aPolishchuk, Nikita$$b2
000302294 7001_ $$00000-0003-2071-322X$$aMayevska, Oksana$$b3
000302294 7001_ $$00000-0001-7803-3900$$aShuvayeva, Galyna$$b4
000302294 7001_ $$aDemir, Melike$$b5
000302294 7001_ $$aLukiyanchuk, Vasyl$$b6
000302294 7001_ $$00000-0003-3912-6594$$aKunz-Schughart, Leoni A$$b7
000302294 7001_ $$00000-0002-3375-1500$$aDubrovska, Anna$$b8
000302294 7001_ $$00000-0001-8135-6102$$aStasyk, Oleh$$b9
000302294 773__ $$0PERI:(DE-600)2701262-1$$a10.3390/biom15060900$$gVol. 15, no. 6, p. 900 -$$n6$$p900$$tBiomolecules$$v15$$x2218-273X$$y2025
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