Increasing sensitivity to DNA damage is a potential driver for human ovarian cancer

Jin, Yimei; Xu, Xin; Wang, Xuemeng; Kuang, Henry; Osterman, Michael D.; Feng, Shi Ting; Han, Deqiang; Wu, Yu; Li, Mo; Guo, Hongyan

doi:10.18632/oncotarget.10436

Cited by 8 publications

(5 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Single-cell gel electrophoretic comet assay was performed under neutral conditions to detect DSBs as described previously (Jin et al , 2016 ). Intact AGS cells infected with H. pylori were collected and rinsed twice with ice-cold PBS; 2 × 10 4 cells/mL were combined with 1% LMAgarose at 40°C at a ratio of 1:3 (v/v) and immediately pipetted onto the slides.…”

Section: Methodsmentioning

confidence: 99%

Helicobacter pylori-Induced DNA Damage Is a Potential Driver for Human Gastric Cancer AGS Cells

Shi

Wang

Yanlei

et al. 2019

DNA and Cell Biology

View full text Add to dashboard Cite

Helicobacter pylori is a major cause of gastric cancer. This study was aimed to explore the characteristic of DNA damage induced by H. pylori infection in gastric cancer AGS cells. After infection with H. pylori, the reactive oxygen species (ROS) levels in AGS cells were significantly higher than those in the uninfected cells. Cells with longer comet tails were detected after infection with H. pylori. The number of apurinic/apyrimidinic endonuclease 1- and phosphorylated H2AX-positive cells was significantly increased compared with the number of negative control cells. The expression of pChk1 and pChk2 was significantly upregulated by H. pylori infection. Cell growth was inhibited after H. pylori infection. All these results were dose dependent. The cell alterations were more significant upon infection with H. pylori at a multiplicity of infection (MOI) of 100:1 than at an MOI of 50:1. H. pylori infection can induce DNA single-strand breaks, DNA double-strand breaks, and cell cycle checkpoint activation after ROS generation in the gastric cancer cell line AGS, which is a potential driver for gastric cancer.

show abstract

Section: Methodsmentioning

confidence: 99%

Helicobacter pylori-Induced DNA Damage Is a Potential Driver for Human Gastric Cancer AGS Cells

Shi

Wang

Yanlei

et al. 2019

DNA and Cell Biology

View full text Add to dashboard Cite

show abstract

“…To this end, we co-stained for 53BP1 and PML using immunofluorescence (IF), the colocalization of which has been shown to mark DNA-SCARS . Although DNA-SCARS were detected via colocaliztion, we quantified a non-significant increase in the proportion of cells that harbored three or more 53BP1 foci , perhaps owing to high levels of basal DNA damage associated with HGSOC (Jin et al, 2016;Wang et al, 2017). Lastly, we explored lamin B1 levels, shown to be downregulated in senescent cells (Freund et al, 2012), and found that late passage HGSOC cells strongly downregulate nuclear lamin B1 as compared to their early passage counterparts ( Fig.…”

Section: Hgsoc Primary Cultures Undergo Culture Stress-induced Senescmentioning

confidence: 99%

Cellular senescence is a central response to cytotoxic chemotherapy in high-grade serous ovarian cancer

Calvo

Cheng

Skulimowski

et al. 2018

Preprint

View full text Add to dashboard Cite

High-grade serous ovarian cancer (HGSOC) commonly responds to initial therapy, but this response is rarely durable. Understanding cell fate decisions taken by HGSOC cells in response to treatment could guide new therapeutic opportunities. Here we find that primary HGSOC cultures undergo therapy-induced senescence (TIS) in response to DNA damage induced by chemotherapy. HGSOC-TIS displays most senescence hallmarks including persistent DNA damage, senescence-associated inflammatory secretome, and selective sensitivity to senolytic Bcl-2 family inhibitors, suggesting avenues for preferential synergistic clearance of these cells. Comparison of pre-and post-chemotherapy HGSOC patient tissue samples revealed changes in senescence biomarkers suggestive of post-treatment "in patient" TIS, and a stronger TIS response in post-chemotherapy tissues correlated with better 5-year survival rates for patients. Together, these data suggest that the induction of cellular senescence in HGSOC cells accounts at least in part for beneficial cellular responses to treatment in patients providing a new therapeutic target. (148/150 words) One Sentence Summary: Cellular senescence is a central beneficial response to chemotherapy in high-grade serous ovarian cancer both in vitro and in patient. Calvo et al. / 2018 3/36

show abstract

“…Decreased expression of the NHEJ core factors has been found to result in increased responsiveness to cancer treatments. Ovarian cancer tissues that showed decreased Ku70 expression were hypersensitive to DNA damage and showed increased cell killing with low doses of IR with the addition of two PARP inhibitors (PJ34 and olaparib) [ 186 ]. In cervical carcinomas, a correlation between measurements of tumor radiosensitivity and Ku70 expression was found, as all tumors with a lower number of Ku70- or Ku80-positive cells were radiosensitive [ 187 ].…”

Section: Core Nhej Factors In Carcinogenesis and Cancermentioning

confidence: 99%

The Role of the Core Non-Homologous End Joining Factors in Carcinogenesis and Cancer

Sishc

Davis

2017

Cancers

139

View full text Add to dashboard Cite

DNA double-strand breaks (DSBs) are deleterious DNA lesions that if left unrepaired or are misrepaired, potentially result in chromosomal aberrations, known drivers of carcinogenesis. Pathways that direct the repair of DSBs are traditionally believed to be guardians of the genome as they protect cells from genomic instability. The prominent DSB repair pathway in human cells is the non-homologous end joining (NHEJ) pathway, which mediates template-independent re-ligation of the broken DNA molecule and is active in all phases of the cell cycle. Its role as a guardian of the genome is supported by the fact that defects in NHEJ lead to increased sensitivity to agents that induce DSBs and an increased frequency of chromosomal aberrations. Conversely, evidence from tumors and tumor cell lines has emerged that NHEJ also promotes chromosomal aberrations and genomic instability, particularly in cells that have a defect in one of the other DSB repair pathways. Collectively, the data present a conundrum: how can a single pathway both suppress and promote carcinogenesis? In this review, we will examine NHEJ’s role as both a guardian and a disruptor of the genome and explain how underlying genetic context not only dictates whether NHEJ promotes or suppresses carcinogenesis, but also how it alters the response of tumors to conventional therapeutics.

show abstract

Increasing sensitivity to DNA damage is a potential driver for human ovarian cancer

Cited by 8 publications

References 69 publications

Helicobacter pylori-Induced DNA Damage Is a Potential Driver for Human Gastric Cancer AGS Cells

Helicobacter pylori-Induced DNA Damage Is a Potential Driver for Human Gastric Cancer AGS Cells

Cellular senescence is a central response to cytotoxic chemotherapy in high-grade serous ovarian cancer

The Role of the Core Non-Homologous End Joining Factors in Carcinogenesis and Cancer

Contact Info

Product

Resources

About