scholarly journals Di-(2-ethylhexyl) phthalate-induced tumor growth is regulated by primary cilium formation via the axis of H2O2 production-thymosin beta-4 gene expression

2021 ◽  
Vol 18 (5) ◽  
pp. 1247-1258
Author(s):  
Jae-Wook Lee ◽  
Pham Xuan Thuy ◽  
Hae-Kyoung Han ◽  
Eun-Yi Moon
Keyword(s):  
Gene Expression ◽  
Tumor Growth ◽  
Primary Cilium ◽  
H2o2 Production ◽  
Thymosin Beta 4 ◽  
Cilium Formation ◽  
Ethylhexyl Phthalate

scholarly journals Deuterium Oxide (D2O) Induces Early Stress Response Gene Expression and Impairs Growth and Metastasis of Experimental Malignant Melanoma

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 605
Author(s):  
Jana Jandova ◽  
Anh B. Hua ◽  
Jocelyn Fimbres ◽  
Georg T. Wondrak
Keyword(s):  
Gene Expression ◽  
Stress Response ◽  
Malignant Melanoma ◽  
Tumor Growth ◽  
Deuterium Oxide ◽  
Human Melanoma ◽  
Pharmacological Intervention ◽  
Melanoma Metastasis ◽  
Response Gene ◽  
Stress Response Gene

There are two stable isotopes of hydrogen, protium (1H) and deuterium (2H; D). Cellular stress response dysregulation in cancer represents both a major pathological driving force and a promising therapeutic target, but the molecular consequences and potential therapeutic impact of deuterium (2H)-stress on cancer cells remain largely unexplored. We have examined the anti-proliferative and apoptogenic effects of deuterium oxide (D2O; ‘heavy water’) together with stress response gene expression profiling in panels of malignant melanoma (A375V600E, A375NRAS, G361, LOX-IMVI), and pancreatic ductal adenocarcinoma (PANC-1, Capan-2, or MIA PaCa-2) cells with inclusion of human diploid Hs27 skin fibroblasts. Moreover, we have examined the efficacy of D2O-based pharmacological intervention in murine models of human melanoma tumor growth and metastasis. D2O-induction of apoptosis was substantiated by AV-PI flow cytometry, immunodetection of PARP-1, and pro-caspase 3 cleavage, and rescue by pan-caspase inhibition. Differential array analysis revealed early modulation of stress response gene expression in both A375 melanoma and PANC-1 adenocarcinoma cells elicited by D2O (90%; ≤6 h) (upregulated: CDKN1A, DDIT3, EGR1, GADD45A, HMOX1, NFKBIA, or SOD2 (up to 9-fold; p < 0.01)) confirmed by independent RT-qPCR analysis. Immunoblot analysis revealed rapid onset of D2O-induced stress response phospho-protein activation (p-ERK, p-JNK, p-eIF2α, or p-H2AX) or attenuation (p-AKT). Feasibility of D2O-based chemotherapeutic intervention (drinking water (30% w/w)) was demonstrated in a severe combined immunodeficiency (SCID) mouse melanoma metastasis model using luciferase-expressing A375-Luc2 cells. Lung tumor burden (visualized by bioluminescence imaging) was attenuated by D2O, and inhibition of invasiveness was also confirmed in an in vitro Matrigel transwell invasion assay. D2O supplementation also suppressed tumor growth in a murine xenograft model of human melanoma, and median survival was significantly increased without causing adverse effects. These data demonstrate for the first time that systemic D2O administration impairs growth and metastasis of malignant melanoma through the pharmacological induction of deuterium (2H)-stress.

scholarly journals Regulation of human glioma cell migration, tumor growth, and stemness gene expression using a Lck targeted inhibitor

Oncogene ◽  
2018 ◽  
Vol 38 (10) ◽  
pp. 1734-1750 ◽  
Author(s):  
J. P. Zepecki ◽  
K. M. Snyder ◽  
M. M. Moreno ◽  
E. Fajardo ◽  
A. Fiser ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Migration ◽  
Tumor Growth ◽  
Glioma Cell ◽  
Human Glioma ◽  
Human Glioma Cell ◽  
Glioma Cell Migration

scholarly journals Small-molecule inhibitor of AF9/ENL-DOT1L/AF4/AFF4 interactions suppresses malignant gene expression and tumor growth

Theranostics ◽  
2021 ◽  
Vol 11 (17) ◽  
pp. 8172-8184
Author(s):  
Fangrui Wu ◽  
Shenyou Nie ◽  
Yuan Yao ◽  
Tong Huo ◽  
Xin Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Growth ◽  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Molecule Inhibitor

scholarly journals A Model for Primary Cilium Biogenesis by Polarized Epithelial Cells: Role of the Midbody Remnant and Associated Specialized Membranes

2021 ◽  
Vol 8 ◽  
Author(s):  
Leticia Labat-de-Hoz ◽  
Armando Rubio-Ramos ◽  
Javier Casares-Arias ◽  
Miguel Bernabé-Rubio ◽  
Isabel Correas ◽  
...  
Keyword(s):  
Cell Surface ◽  
Primary Cilium ◽  
Primary Cilia ◽  
Control Cell ◽  
Future Research ◽  
Alternative Route ◽  
Ciliary Membrane ◽  
Cilium Formation ◽  
Membrane Compartmentalization

Primary cilia are solitary, microtubule-based protrusions surrounded by a ciliary membrane equipped with selected receptors that orchestrate important signaling pathways that control cell growth, differentiation, development and homeostasis. Depending on the cell type, primary cilium assembly takes place intracellularly or at the cell surface. The intracellular route has been the focus of research on primary cilium biogenesis, whereas the route that occurs at the cell surface, which we call the “alternative” route, has been much less thoroughly characterized. In this review, based on recent experimental evidence, we present a model of primary ciliogenesis by the alternative route in which the remnant of the midbody generated upon cytokinesis acquires compact membranes, that are involved in compartmentalization of biological membranes. The midbody remnant delivers part of those membranes to the centrosome in order to assemble the ciliary membrane, thereby licensing primary cilium formation. The midbody remnant's involvement in primary cilium formation, the regulation of its inheritance by the ESCRT machinery, and the assembly of the ciliary membrane from the membranes originally associated with the remnant are discussed in the context of the literature concerning the ciliary membrane, the emerging roles of the midbody remnant, the regulation of cytokinesis, and the role of membrane compartmentalization. We also present a model of cilium emergence during evolution, and summarize the directions for future research.

Pharmacological Regulation of Primary Cilium Formation Affects the Mechanosensitivity of Osteocytes

2020 ◽  
Vol 107 (6) ◽  
pp. 625-635
Author(s):  
Dong Ding ◽  
Xiao Yang ◽  
Hui-qin Luan ◽  
Xin-tong Wu ◽  
Cai He ◽  
...  
Keyword(s):  
Primary Cilium ◽  
Cilium Formation ◽  
Pharmacological Regulation

Glial-specific retrovirally mediated gas1 gene expression induces glioma cell apoptosis and inhibits tumor growth in vivo

2004 ◽  
Vol 15 (3) ◽  
pp. 483-491 ◽  
Author(s):  
Absalom Zamorano ◽  
Britt Mellström ◽  
Paula Vergara ◽  
José R Naranjo ◽  
José Segovia
Keyword(s):  
Gene Expression ◽  
Tumor Growth ◽  
Cell Apoptosis ◽  
Glioma Cell
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