scholarly journals HIF-1 — A BIG CHAPTER IN THE CANCER TALE

2016 ◽  
Vol 38 (1) ◽  
pp. 9-12 ◽  
Author(s):  
J Ajdukovic
Keyword(s):  
Tumor Suppressor ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Tumor Suppressor Genes ◽  
Biological Effects ◽  
Hypoxia Inducible Factor ◽  
Signal Molecules ◽  
Suppressor Genes ◽  
Carcinoma Associated Fibroblasts

Approximately 1.0–1.5% of the genome is transcriptionally regulated by hypoxia, and hypoxia-inducible factor (HIF)-1α is the transcription factor modulating many of these genes. Cancer cells are able to survive hypoxic environments and hypoxia itself can activate adaptive cellular responses that contribute to tumor progression. Many HIF-1α-mediated biological effects are beneficial for tumor progression, including metabolic shift toward glycolysis, inhibition of fatty acid β-oxidation, production of cellular reacreactive oxygen species and altering expression of tumor suppressor genes. HIF-1 promotes selective mitochondrial autophagy, resisand altering expression of tumor suppressor genes. HIF-1 promotes selective mitochondrial autophagy, resistance to T cell mediated lysis of cancer cells, induction of pluripotent cancer stem cells, epithelial-mesenchymal and epithelialmesenchymal-endothelial transitions beneficial for tumor growth and progression, loss of E-cadherin. HIF-1 also induces production of signal molecules and cytokines by carcinoma-associated fibroblasts and upregulation of certain microRNAs important for cancer progression. This minireview focuses on the HIF-1 promoting role in tumor initiation and progression and HIF-1 targeting. HIF-1 pathway downregulation seems to be promising in future cancer treatment.

Up-regulation of tumor suppressor genes might promote the malignant phenotype of cancer cells

2007 ◽  
Vol 69 (6) ◽  
pp. 1379 ◽  
Author(s):  
Liu Hong ◽  
Xiaohua Li ◽  
Haifeng Jin ◽  
Li Yan ◽  
Kaichun Wu ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cancer Cells ◽  
Tumor Suppressor Genes ◽  
Malignant Phenotype ◽  
Suppressor Genes

scholarly journals Thymoquinone-Induced Reactivation of Tumor Suppressor Genes in Cancer Cells Involves Epigenetic Mechanisms

2019 ◽  
Vol 12 ◽  
pp. 251686571983901 ◽  
Author(s):  
Shahad A Qadi ◽  
Mohammed A Hassan ◽  
Ryan A Sheikh ◽  
Othman AS Baothman ◽  
Mazin A Zamzami ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Cell Line ◽  
Rna Sequencing ◽  
Cancer Cell ◽  
Tumor Suppressor Genes ◽  
Jurkat Cells ◽  
Leukemia Cell Line ◽  
Suppressor Genes

The epigenetic silencing of tumor suppressor genes (TSGs) is a common finding in several solid and hematological tumors involving various epigenetic readers and writers leading to enhanced cell proliferation and defective apoptosis. Thymoquinone (TQ), the major biologically active compound of black seed oil, has demonstrated anticancer activities in various tumors by targeting several pathways. However, its effects on the epigenetic code of cancer cells are largely unknown. In the present study, we performed RNA sequencing to investigate the anticancer mechanisms of TQ-treated T-cell acute lymphoblastic leukemia cell line (Jurkat cells) and examined gene expression using different tools. We found that many key epigenetic players, including ubiquitin-like containing plant homeodomain (PHD) and really interesting new gene (RING) finger domains 1 ( UHRF1), DNMT1,3A,3B, G9A, HDAC1,4,9, KDM1B, and KMT2A,B,C,D,E, were downregulated in TQ-treated Jurkat cells. Interestingly, several TSGs, such as DLC1, PPARG, ST7, FOXO6, TET2, CYP1B1, SALL4, and DDIT3, known to be epigenetically silenced in various tumors, including acute leukemia, were upregulated, along with the upregulation of several downstream pro-apoptotic genes, such as RASL11B, RASD1, GNG3, BAD, and BIK. Data obtained from RNA sequencing were confirmed using quantitative reverse transcription polymerase chain reaction (RT-qPCR) in Jurkat cells, as well as in a human breast cancer cell line (MDA-MB-468 cells). We found that the decrease in cell proliferation and in the expression of UHRF1, DNMT1, G9a, and HDAC1 genes in both cancer cell (Jurkat cells and MDA-MB-468 cells) lines depends on the TQ dose. Our results indicate that the use of TQ as an epigenetic drug represents a promising strategy for epigenetic therapy for both solid and blood tumors by targeting both DNA methylation and histone post-translational modifications.

scholarly journals Genetic and Biochemical Evidence That Haploinsufficiency of the Nf1 Tumor Suppressor Gene Modulates Melanocyte and Mast Cell Fates in Vivo

2000 ◽  
Vol 191 (1) ◽  
pp. 181-188 ◽  
Author(s):  
David A. Ingram ◽  
Feng-Chun Yang ◽  
Jeffrey B. Travers ◽  
Mary Jo Wenning ◽  
Kelly Hiatt ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Biological Effects ◽  
Malignant Neoplasms ◽  
Protein Kinase Activity ◽  
Cell Fates ◽  
Suppressor Genes

Neurofibromatosis type 1 (NF1) is a common autosomal-dominant disorder characterized by cutaneous neurofibromas infiltrated with large numbers of mast cells, melanocyte hyperplasia, and a predisposition to develop malignant neoplasms. NF1 encodes a GTPase activating protein (GAP) for Ras. Consistent with Knudson's “two hit” model of tumor suppressor genes, leukemias and malignant solid tumors in NF1 patients frequently demonstrate somatic loss of the normal NF1 allele. However, the phenotypic and biochemical consequences of heterozygous inactivation of Nf1 are largely unknown. Recently neurofibromin, the protein encoded by NF1, was shown to negatively regulate Ras activity in Nf1−/− murine myeloid hematopoietic cells in vitro through the c-kit receptor tyrosine kinase (dominant white spotting, W). Since the W and Nf1 locus appear to function along a common developmental pathway, we generated mice with mutations at both loci to examine potential interactions in vivo. Here, we show that haploinsufficiency at Nf1 perturbs cell fates in mast cells in vivo, and partially rescues coat color and mast cell defects in W41 mice. Haploinsufficiency at Nf1 also increased mast cell proliferation, survival, and colony formation in response to Steel factor, the ligand for c-kit. Furthermore, haploinsufficiency was associated with enhanced Ras–mitogen-activated protein kinase activity, a major downstream effector of Ras, via wild-type and mutant (W41) c-kit receptors. These observations identify a novel interaction between c-kit and neurofibromin in vivo, and offer experimental evidence that haploinsufficiency of Nf1 alters both cellular and biochemical phenotypes in two cell lineages that are affected in individuals with NF1. Collectively, these data support the emerging concept that heterozygous inactivation of tumor suppressor genes may have profound biological effects in multiple cell types.

scholarly journals KMT2D inhibits the growth and metastasis of bladder Cancer cells by maintaining the tumor suppressor genes

2019 ◽  
Vol 115 ◽  
pp. 108924 ◽  
Author(s):  
Peng Sun ◽  
Tong Wu ◽  
Xiaoliang Sun ◽  
Zilian Cui ◽  
Haiyang Zhang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Tumor Suppressor Genes ◽  
Suppressor Genes ◽  
Bladder Cancer Cells

scholarly journals CRISPR-mediated modeling and functional validation of candidate tumor suppressor genes in small cell lung cancer

2019 ◽  
Vol 117 (1) ◽  
pp. 513-521 ◽  
Author(s):  
Sheng Rong Ng ◽  
William M. Rideout ◽  
Elliot H. Akama-Garren ◽  
Arjun Bhutkar ◽  
Kim L. Mercer ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Suppressor ◽  
Small Cell Lung Cancer ◽  
Tumor Progression ◽  
Cell Lung Cancer ◽  
Tumor Suppressor Genes ◽  
Small Cell ◽  
Small Cell Lung ◽  
Suppressor Genes ◽  
Sequencing Studies

Small cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer that remains among the most lethal of solid tumor malignancies. Recent genomic sequencing studies have identified many recurrently mutated genes in human SCLC tumors. However, the functional roles of most of these genes remain to be validated. Here, we have adapted the CRISPR-Cas9 system to a well-established murine model of SCLC to rapidly model loss-of-function mutations in candidate genes identified from SCLC sequencing studies. We show that loss of the genep107significantly accelerates tumor progression. Notably, compared with loss of the closely related genep130, loss ofp107results in fewer but larger tumors as well as earlier metastatic spread. In addition, we observe differences in proliferation and apoptosis as well as altered distribution of initiated tumors in the lung, resulting from loss ofp107orp130. Collectively, these data demonstrate the feasibility of using the CRISPR-Cas9 system to model loss of candidate tumor suppressor genes in SCLC, and we anticipate that this approach will facilitate efforts to investigate mechanisms driving tumor progression in this deadly disease.

scholarly journals Cancer cell-selective killing polymer/copper combination

2016 ◽  
Vol 4 (1) ◽  
pp. 115-120 ◽  
Author(s):  
Huacheng He ◽  
Diego Altomare ◽  
Ufuk Ozer ◽  
Hanwen Xu ◽  
Kim Creek ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Tumor Suppressor Genes ◽  
Glutathione Level ◽  
Suppressor Genes

A polymer/copper combination selectively kills cancer cells by targeting their high glutathione level, upregulated oncogenes, and downregulated tumor suppressor genes.

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