scholarly journals Defective IFNα/γ-induced STAT3 protein activation in human malignant melanoma cells

2008 ◽  
Author(s):  
Boudny
Keyword(s):  
Malignant Melanoma ◽  
Melanoma Cells ◽  
Human Malignant Melanoma ◽  
Protein Activation

scholarly journals Toxicogenomics of A375 human malignant melanoma cells treated with arbutin

2006 ◽  
Vol 14 (1) ◽  
pp. 87-105 ◽  
Author(s):  
Sun-Long Cheng ◽  
Rosa Huang Liu ◽  
Jin-Nan Sheu ◽  
Shui-Tein Chen ◽  
Supachok Sinchaikul ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Melanoma Cells ◽  
Human Malignant Melanoma

scholarly journals Beta3-Tubulin Is Critical for Microtubule Dynamics, Cell Cycle Regulation, and Spontaneous Release of Microvesicles in Human Malignant Melanoma Cells (A375)

2020 ◽  
Vol 21 (5) ◽  
pp. 1656
Author(s):  
Mohammed O. Altonsy ◽  
Anutosh Ganguly ◽  
Matthias Amrein ◽  
Philip Surmanowicz ◽  
Shu Shun Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Malignant Melanoma ◽  
Structural Changes ◽  
Melanoma Cells ◽  
Neoplastic Cell ◽  
Primary Component ◽  
Cellular Growth ◽  
Class Iii ◽  
M Cell ◽  
Human Malignant Melanoma

Microtubules (MTs), microfilaments, and intermediate filaments, the main constituents of the cytoskeleton, undergo continuous structural changes (metamorphosis), which are central to cellular growth, division, and release of microvesicles (MVs). Altered MTs dynamics, uncontrolled proliferation, and increased production of MVs are hallmarks of carcinogenesis. Class III beta-tubulin (β3-tubulin), one of seven β-tubulin isotypes, is a primary component of MT, which correlates with enhanced neoplastic cell survival, metastasis and resistance to chemotherapy. We studied the effects of β3-tubulin gene silencing on MTs dynamics, cell cycle, and MVs release in human malignant melanoma cells (A375). The knockdown of β3-tubulin induced G2/M cell cycle arrest, impaired MTs dynamics, and reduced spontaneous MVs release. Additional studies are therefore required to elucidate the pathophysiologic and therapeutic role of β3-tubulin in melanoma.

scholarly journals Genetic Target Modulation Employing CRISPR/Cas9 Identifies Glyoxalase 1 as a Novel Molecular Determinant of Invasion and Metastasis in A375 Human Malignant Melanoma Cells In Vitro and In Vivo

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1369 ◽  
Author(s):  
Jana Jandova ◽  
Jessica Perer ◽  
Anh Hua ◽  
Jeremy A. Snell ◽  
Georg T. Wondrak
Keyword(s):  
Malignant Melanoma ◽  
Enzymatic Activity ◽  
Melanoma Cell ◽  
Melanoma Cells ◽  
Metabolic Reprogramming ◽  
Invasion And Metastasis ◽  
Genetic Rescue ◽  
Human Malignant Melanoma ◽  
Glyoxalase 1 ◽  
Molecular Determinant

Metabolic reprogramming is a molecular hallmark of cancer. Recently, we have reported the overexpression of glyoxalase 1 (encoded by GLO1), a glutathione-dependent enzyme involved in detoxification of the reactive glycolytic byproduct methylglyoxal, in human malignant melanoma cell culture models and clinical samples. However, the specific role of GLO1 in melanomagenesis remains largely unexplored. Here, using genetic target modulation, we report the identification of GLO1 as a novel molecular determinant of invasion and metastasis in malignant melanoma. First, A375 human malignant melanoma cells with GLO1 deletion (A375-GLO1_KO) were engineered using CRISPR/Cas9, and genetic rescue clones were generated by stable transfection of KO clones employing a CMV-driven GLO1 construct (A375-GLO1_R). After confirming GLO1 target modulation at the mRNA and protein levels (RT-qPCR, immunodetection, enzymatic activity), phenotypic characterization indicated that deletion of GLO1 does not impact proliferative capacity while causing significant sensitization to methylglyoxal-, chemotherapy-, and starvation-induced cytotoxic stress. Employing differential gene expression array analysis (A375-GLO1_KO versus A375-GLO1_WT), pronounced modulation of epithelial mesenchymal transition (EMT)-related genes [upregulated: CDH1, OCLN, IL1RN, PDGFRB, SNAI3; (downregulated): BMP1, CDH2, CTNNB1, FN1, FTH1, FZD7, MELTF, MMP2, MMP9, MYC, PTGS2, SNAI2, TFRC, TWIST1, VIM, WNT5A, ZEB1, and ZEB2 (up to tenfold; p < 0.05)] was observed—all of which are consistent with EMT suppression as a result of GLO1 deletion. Importantly, these expression changes were largely reversed upon genetic rescue employing A375-GLO1_R cells. Differential expression of MMP9 as a function of GLO1 status was further substantiated by enzymatic activity and ELISA analysis; phenotypic assessment revealed the pronounced attenuation of morphological potential, transwell migration, and matrigel 3D-invasion capacity displayed by A375-GLO1_KO cells, reversed again in genetic rescue clones. Strikingly, in a SCID mouse metastasis model, lung tumor burden imposed by A375-GLO1_KO cells was strongly attenuated as compared to A375-GLO1_WT cells. Taken together, these prototype data provide evidence in support of a novel function of GLO1 in melanoma cell invasiveness and metastasis, and ongoing investigations explore the function and therapeutic potential of GLO1 as a novel melanoma target.

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