PARP1 blockade is synthetically lethal in XRCC1 deficient sporadic epithelial ovarian cancers

Ali, Reem; Alabdullah, Muslim; Alblihy, Adel; Miligy, Islam M.; Mesquita, Katia A.; Chan, Stephen Y.; Moseley, Paul M.; Rakha, Emad A.

doi:10.1016/j.canlet.2019.10.035

Cited by 25 publications

(34 citation statements)

References 35 publications

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“…e Radius TM 24-well cell migration assay (Cell Biolabs, Inc., San Diego, CA, USA) was used to study cell migration and invasion [20]. To determine cell migration, we put the 0.5 mL of solution A (gel pretreatment) on every place.…”

Section: Cell Migration and Invasion Testmentioning

confidence: 99%

The Effect of Suppression Taurine on Relocation and Epithelial-Mesenchymal Transition in Mankind Lung Cancer Cells

Deng

Tang

2021

Journal of Healthcare Engineering

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Aim. Taurine is believed to have antioxidant properties and has been implicated in the treatment of neurodegenerative disease, atherosclerosis, coronary heart disease, and prostate cancer. This research focused on taurine inhibition effects of expression related to migration and epithelial-mesenchymal transition- (EMT-) A549 study on related genes of human being non-small-cell lung cancer. Methods. MTT assays assessed cell viability and a RadiusTM assay showed that taurine also inhibited the lung cancer cell migration. Using RT-PCR and Western blot, the migration and EMT markers were identified and evaluated. Results. We found that taurine significantly decreased the expression of migration markers matrix metallopeptidase 9 (MMP-9) and vascular endothelial growth factor (VEGF). In contrast, TIMP metallopeptidase inhibitor 1 (TIMP-1) and TIMP metallopeptidase inhibitor 2 (TIMP-2) expressions were increased with taurine treatment. In addition, we found an association between taurine treatment and the expression of EMT markers. The expression of epithelial marker E-cadherin and the mesenchymal marker N-cadherin TWIST-1 was decreased, but the expression of zinc finger protein SNAIL-1 and E-zinc finger homeobox 1 (ZEB-1) was increased. Conclusion. Taken together, our study strongly suggests the therapeutic significance of taurine, which possesses antimigration activity and induces EMT markers expression in lung cancer cells.

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Section: Cell Migration and Invasion Testmentioning

confidence: 99%

The Effect of Suppression Taurine on Relocation and Epithelial-Mesenchymal Transition in Mankind Lung Cancer Cells

Deng

Tang

2021

Journal of Healthcare Engineering

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“…The balance between PARP1 and XRCC1 expression might modulate response to PARP1. Previous studies in other cancer types have reported the efficient targeting of PARP1 in XRCC1 deficient lines [ 40 , 41 , 42 ]. In our study, the most sensitive cell to PARP1 blockade, e.g., BT83, displayed PARP1 expression and concomitant absence of XRCC1 protein/mRNA expressions.…”

Section: Discussionmentioning

confidence: 99%

A DNA Repair and Cell Cycle Gene Expression Signature in Pediatric High-Grade Gliomas: Prognostic and Therapeutic Value

Entz‐Werlé¹,

Poidevin

Nazarov

et al. 2021

Cancers

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Background: Pediatric high-grade gliomas (pHGGs) are the leading cause of mortality in pediatric neuro-oncology, displaying frequent resistance to standard therapies. Profiling DNA repair and cell cycle gene expression has recently been proposed as a strategy to classify adult glioblastomas. To improve our understanding of the DNA damage response pathways that operate in pHGGs and the vulnerabilities that these pathways might expose, we sought to identify and characterize a specific DNA repair and cell-cycle gene expression signature of pHGGs. Methods: Transcriptomic analyses were performed to identify a DNA repair and cell-cycle gene expression signature able to discriminate pHGGs (n = 6) from low-grade gliomas (n = 10). This signature was compared to related signatures already established. We used the pHGG signature to explore already transcriptomic datasets of DIPGs and sus-tentorial pHGGs. Finally, we examined the expression of key proteins of the pHGG signature in 21 pHGG diagnostic samples and nine paired relapses. Functional inhibition of one DNA repair factor was carried out in four patients who derived H3.3 K27M mutant cell lines. Results: We identified a 28-gene expression signature of DNA repair and cell cycle that clustered pHGGs cohorts, in particular sus-tentorial locations, in two groups. Differential protein expression levels of PARP1 and XRCC1 were associated to TP53 mutations and TOP2A amplification and linked significantly to the more radioresistant pHGGs displaying the worst outcome. Using patient-derived cell lines, we showed that the PARP-1/XRCC1 expression balance might be correlated with resistance to PARP1 inhibition. Conclusion: We provide evidence that PARP1 overexpression, associated to XRCC1 expression, TP53 mutations, and TOP2A amplification, is a new theranostic and potential therapeutic target.

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“…PARP-2 -deficient mouse embryonic fibroblast cells displayed a delay in DNA strand break repair similar to PARP-1 deficient cells [ 167 ]. PARP-1 blockades are synthetically lethal in XRCC1-deficient sporadic ovarian carcinoma and ductal breast carcinoma [ 168 , 169 ]. However, PARP1 and PARP2 still regulate two different yet connected aspects of DNA base damage tolerance.…”

Section: Parps In Hallmark Cancer Traitsmentioning

confidence: 99%

The PARP Enzyme Family and the Hallmarks of Cancer Part 1. Cell Intrinsic Hallmarks

Demény

Virág

2021

Cancers

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The 17-member poly (ADP-ribose) polymerase enzyme family, also known as the ADP-ribosyl transferase diphtheria toxin-like (ARTD) enzyme family, contains DNA damage-responsive and nonresponsive members. Only PARP1, 2, 5a, and 5b are capable of modifying their targets with poly ADP-ribose (PAR) polymers; the other PARP family members function as mono-ADP-ribosyl transferases. In the last decade, PARP1 has taken center stage in oncology treatments. New PARP inhibitors (PARPi) have been introduced for the targeted treatment of breast cancer 1 or 2 (BRCA1/2)-deficient ovarian and breast cancers, and this novel therapy represents the prototype of the synthetic lethality paradigm. Much less attention has been paid to other PARPs and their potential roles in cancer biology. In this review, we summarize the roles played by all PARP enzyme family members in six intrinsic hallmarks of cancer: uncontrolled proliferation, evasion of growth suppressors, cell death resistance, genome instability, reprogrammed energy metabolism, and escape from replicative senescence. In a companion paper, we will discuss the roles of PARP enzymes in cancer hallmarks related to cancer-host interactions, including angiogenesis, invasion and metastasis, evasion of the anticancer immune response, and tumor-promoting inflammation. While PARP1 is clearly involved in all ten cancer hallmarks, an increasing body of evidence supports the role of other PARPs in modifying these cancer hallmarks (e.g., PARP5a and 5b in replicative immortality and PARP2 in cancer metabolism). We also highlight controversies, open questions, and discuss prospects of recent developments related to the wide range of roles played by PARPs in cancer biology. Some of the summarized findings may explain resistance to PARPi therapy or highlight novel biological roles of PARPs that can be therapeutically exploited in novel anticancer treatment paradigms.

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PARP1 blockade is synthetically lethal in XRCC1 deficient sporadic epithelial ovarian cancers

Cited by 25 publications

References 35 publications

The Effect of Suppression Taurine on Relocation and Epithelial-Mesenchymal Transition in Mankind Lung Cancer Cells

The Effect of Suppression Taurine on Relocation and Epithelial-Mesenchymal Transition in Mankind Lung Cancer Cells

A DNA Repair and Cell Cycle Gene Expression Signature in Pediatric High-Grade Gliomas: Prognostic and Therapeutic Value

The PARP Enzyme Family and the Hallmarks of Cancer Part 1. Cell Intrinsic Hallmarks

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