scholarly journals Modulation of the E2F1-Driven Cancer Cell Fate by the DNA Damage Response Machinery and Potential Novel E2F1 Targets in Osteosarcomas

2009 ◽  
Vol 175 (1) ◽  
pp. 376-391 ◽  
Author(s):  
Michalis Liontos ◽  
Katerina Niforou ◽  
Georgia Velimezi ◽  
Konstantinos Vougas ◽  
Konstantinos Evangelou ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Fate ◽  
Cancer Cell ◽  
Dna Damage Response ◽  
Damage Response

scholarly journals NKX3.1 contributes to S phase entry and regulates DNA damage response (DDR) in prostate cancer cell lines

2011 ◽  
Vol 414 (1) ◽  
pp. 123-128 ◽  
Author(s):  
Burcu Erbaykent-Tepedelen ◽  
Besra Özmen ◽  
Lokman Varisli ◽  
Ceren Gonen-Korkmaz ◽  
Bilge Debelec-Butuner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Damage ◽  
Cell Lines ◽  
Cancer Cell ◽  
Dna Damage Response ◽  
Prostate Cancer Cell ◽  
S Phase ◽  
Prostate Cancer Cell Lines ◽  
Damage Response ◽  
Phase Entry

scholarly journals Dysregulation of hsa-miR-34a and hsa-miR-449a leads to overexpression of PACS-1 and loss of DNA damage response (DDR) in cervical cancer

2020 ◽  
Vol 295 (50) ◽  
pp. 17169-17186
Author(s):  
Mysore S. Veena ◽  
Santanu Raychaudhuri ◽  
Saroj K. Basak ◽  
Natarajan Venkatesan ◽  
Parameet Kumar ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Dna Damage ◽  
Cell Growth ◽  
Cell Lines ◽  
Cancer Cell ◽  
Dna Damage Response ◽  
S Phase ◽  
Cervical Cancer Cell ◽  
Damage Response

We have observed overexpression of PACS-1, a cytosolic sorting protein in primary cervical tumors. Absence of exonic mutations and overexpression at the RNA level suggested a transcriptional and/or posttranscriptional regulation. University of California Santa Cruz genome browser analysis of PACS-1 micro RNAs (miR), revealed two 8-base target sequences at the 3′ terminus for hsa-miR-34a and hsa-miR-449a. Quantitative RT-PCR and Northern blotting studies showed reduced or loss of expression of the two microRNAs in cervical cancer cell lines and primary tumors, indicating dysregulation of these two microRNAs in cervical cancer. Loss of PACS-1 with siRNA or exogenous expression of hsa-miR-34a or hsa-miR-449a in HeLa and SiHa cervical cancer cell lines resulted in DNA damage response, S-phase cell cycle arrest, and reduction in cell growth. Furthermore, the siRNA studies showed that loss of PACS-1 expression was accompanied by increased nuclear γH2AX expression, Lys382-p53 acetylation, and genomic instability. PACS-1 re-expression through LNA-hsa-anti-miR-34a or -449a or through PACS-1 cDNA transfection led to the reversal of DNA damage response and restoration of cell growth. Release of cells post 24-h serum starvation showed PACS-1 nuclear localization at G1-S phase of the cell cycle. Our results therefore indicate that the loss of hsa-miR-34a and hsa-miR-449a expression in cervical cancer leads to overexpression of PACS-1 and suppression of DNA damage response, resulting in the development of chemo-resistant tumors.

scholarly journals Cellular responses to a prolonged delay in mitosis are determined by a DNA damage response controlled by Bcl-2 family proteins

Open Biology ◽  
2015 ◽  
Vol 5 (3) ◽  
pp. 140156 ◽  
Author(s):  
Didier J. Colin ◽  
Karolina O. Hain ◽  
Lindsey A. Allan ◽  
Paul R. Clarke
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Protein Kinases ◽  
Cell Fate ◽  
Dna Damage Response ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Anti Cancer ◽  
Damage Response ◽  
Microtubule Poisons

Anti-cancer drugs that disrupt mitosis inhibit cell proliferation and induce apoptosis, although the mechanisms of these responses are poorly understood. Here, we characterize a mitotic stress response that determines cell fate in response to microtubule poisons. We show that mitotic arrest induced by these drugs produces a temporally controlled DNA damage response (DDR) characterized by the caspase-dependent formation of γH2AX foci in non-apoptotic cells. Following exit from a delayed mitosis, this initial response results in activation of DDR protein kinases, phosphorylation of the tumour suppressor p53 and a delay in subsequent cell cycle progression. We show that this response is controlled by Mcl-1, a regulator of caspase activation that becomes degraded during mitotic arrest. Chemical inhibition of Mcl-1 and the related proteins Bcl-2 and Bcl-x L by a BH3 mimetic enhances the mitotic DDR, promotes p53 activation and inhibits subsequent cell cycle progression. We also show that inhibitors of DDR protein kinases as well as BH3 mimetics promote apoptosis synergistically with taxol (paclitaxel) in a variety of cancer cell lines. Our work demonstrates the role of mitotic DNA damage responses in determining cell fate in response to microtubule poisons and BH3 mimetics, providing a rationale for anti-cancer combination chemotherapies.

scholarly journals Autophagy Roles in Genome Maintenance

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1793 ◽  
Author(s):  
Susanna Ambrosio ◽  
Barbara Majello
Keyword(s):  
Dna Damage ◽  
Cell Fate ◽  
Dna Damage Response ◽  
Current Knowledge ◽  
Response To Therapy ◽  
Genome Integrity ◽  
Genome Maintenance ◽  
Damage Response ◽  
Cancer Cell Survival ◽  
Fate Decision

In recent years, a considerable correlation has emerged between autophagy and genome integrity. A range of mechanisms appear to be involved where autophagy participates in preventing genomic instability, as well as in DNA damage response and cell fate decision. These initial findings have attracted particular attention in the context of malignancy; however, the crosstalk between autophagy and DNA damage response is just beginning to be explored and key questions remain that need to be addressed, to move this area of research forward and illuminate the overall consequence of targeting this process in human therapies. Here we present current knowledge on the complex crosstalk between autophagy and genome integrity and discuss its implications for cancer cell survival and response to therapy.

scholarly journals TFEB Modulates p21/WAF1/CIP1 during the DNA Damage Response

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1186 ◽  
Author(s):  
Sandra Pisonero-Vaquero ◽  
Chiara Soldati ◽  
Marcella Cesana ◽  
Andrea Ballabio ◽  
Diego Luis Medina
Keyword(s):  
Dna Damage ◽  
Cancer Cell ◽  
Dna Damage Response ◽  
Cell Types ◽  
Dependent Manner ◽  
Cancer Cell Growth ◽  
Direct Role ◽  
Growth And Survival ◽  
Damage Response ◽  
P21 Waf1

The MiT/TFE family of transcription factors (MITF, TFE3, and TFEB), which control transcriptional programs for autophagy and lysosome biogenesis have emerged as regulators of energy metabolism in cancer. Thus, their activation increases lysosomal catabolic function to sustain cancer cell growth and survival in stress conditions. Here, we found that TFEB depletion dramatically reduces basal expression levels of the cyclin-dependent kinase (CDK) inhibitor p21/WAF1 in various cell types. Conversely, TFEB overexpression increases p21 in a p53-dependent manner. Furthermore, induction of DNA damage using doxorubicin induces TFEB-mediated activation of p21, delays G2/M phase arrest, and promotes cell survival. Pharmacological inhibition of p21, instead, abrogates TFEB-mediated protection during the DNA damage response. Together, our findings uncover a novel and direct role of TFEB in the regulation of p21 expression in both steady-state conditions and during the induction of DNA-damage response (DDR). Our observations might open novel therapeutic strategies to promote cancer cell death by targeting the TFEB-p21 pathway in the presence of genotoxic agents.

DNA damage response following X-irradiation in oral cancer cell lines HSC3 and HSC4

2018 ◽  
Vol 90 ◽  
pp. 1-8 ◽  
Author(s):  
Sirimanas Jiaranuchart ◽  
Atsushi Kaida ◽  
Yusuke Onozato ◽  
Hiroyuki Harada ◽  
Masahiko Miura
Keyword(s):  
Dna Damage ◽  
Oral Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Dna Damage Response ◽  
Cancer Cell Lines ◽  
Oral Cancer Cell ◽  
Damage Response ◽  
X Irradiation

scholarly journals The p400/Tip60 ratio is critical for colorectal cancer cell proliferation through DNA damage response pathways

Oncogene ◽  
2009 ◽  
Vol 28 (12) ◽  
pp. 1506-1517 ◽  
Author(s):  
L Mattera ◽  
F Escaffit ◽  
M-J Pillaire ◽  
J Selves ◽  
S Tyteca ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Cancer Cell ◽  
Dna Damage Response ◽  
Colorectal Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Damage Response
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