TopBP1 contributes to the chemoresistance in non-small cell lung cancer through upregulation of p53

Lv, Yinxiang; Huo, Yanyan; Yu, X H; Liu, Rongrong; Zhang, Shufen; Zheng, Xiaoxiao; Zhang, Xianning

doi:10.2147/dddt.s90705

Cited by 15 publications

(10 citation statements)

References 33 publications

(30 reference statements)

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“…On the other hand, ERb1 decreased the viability of chemotherapy-treated H358 cells by inducing apoptosis. H358 cells are more sensitive to doxorubicin than H1299 cells and this may account for the specific action of ERb1 in these cells (58). Upon chemotherapy treatment, the active levels of Chk1 were lower in ERb1-expressing compared with the control H358 cells, suggesting that the receptor abrogates the drug-induced G 2 -M cell-cycle checkpoint.…”

Section: Discussionmentioning

confidence: 98%

ERβ Sensitizes NSCLC to Chemotherapy by Regulating DNA Damage Response

Nikolos

Thomas

Bado

et al. 2018

Molecular Cancer Research

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The expression of wild-type estrogen receptor β (ESR2/ERβ1) correlates with clinical outcome in patients with non-small cell lung cancer (NSCLC). However, the molecular mechanism that accounts for this association is currently poorly understood. ERβ1 was previously linked to chemotherapy response in patients with breast cancer and in breast cancer cells. The effect of the receptor in NSCLC cells after chemotherapy treatment, a common remedy for advanced NSCLC, has not been studied. Here, upregulation of ERβ1 increases the sensitivity of NSCLC cells to treatment with doxorubicin and etoposide. This effect was primarily observed in p53-defecient NSCLC cells. In these cells, ERβ1 either enhanced G-M cell-cycle arrest by activating the checkpoint kinase 1 (Chk1) and altering downstream signaling or induced apoptosis. The expression of p63 target genes that control G-M checkpoint activation was altered by ERβ1 suggesting an ERβ1-p63 transcriptional cooperation in lung cancer cells that affects DNA damage response (DDR). These results suggest involvement of ERβ1 in the mechanism that regulates DNA damage response in NSCLC cells and support the potential predictive and therapeutic value of the receptor in clinical management of the disease. This study demonstrating the impact of ERβ1 on chemosensitivity of NSCLC cells suggests the predictive value of the receptor for successful response of tumors to chemotherapy and the potential benefit of chemotherapy-treated patients from the use of ER ligands. .

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Section: Discussionmentioning

confidence: 98%

ERβ Sensitizes NSCLC to Chemotherapy by Regulating DNA Damage Response

Nikolos

Thomas

Bado

et al. 2018

Molecular Cancer Research

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“…TopBP1-overexpressed tumors show aggressive features such as high-grade breast carcinomas (66.7% vs. 35.5% grade 3; p = .007), advanced sarcomas (hazard ratio for stage III-IV sarcomas, 3.4; 95% CI, 2.0-5.6), lung metastasis (hazard ratio, 5.1; 95% CI, 3.1-8.6), with reduced survival (OS in breast cancer, 40 vs. 165 months; p = .003 and hazard ratio in sarcoma, 2.2; 95% CI, 1.3-3.7) [32][33][34]. Excessive TopBP1 induces chemoresistance against platinum agents, whereas TopBP1 depletion enhances PARPi efficacy by inhibiting RAD51 loading to ssDNA ends [35,36], although TopBP1 has both prognostic and predictive significance, but not cancer predisposition. Karppinen et al identified 19 TopBP1 germline variants in 125 families with breast or ovarian cancers [37].…”

Section: Dna Damage Sensorsmentioning

confidence: 99%

Homologous Recombination Deficiency: Cancer Predispositions and Treatment Implications

Toh

Ngeow

2021

The Oncologist

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Homologous recombination (HR) is a highly accurate DNA repair mechanism. Several HR genes are established cancer susceptibility genes with clinically actionable pathogenic variants (PVs). Classically, BRCA1 and BRCA2 germline PVs are associated with significant breast and ovarian cancer risks. Patients with BRCA1/BRCA2 PVs display worse clinical outcomes but respond better to platinum-based chemotherapies and PARP inhibitors, a trait termed as "BRCAness". With the advent of whole-exome sequencing and multigene panels, PVs in other HR genes are increasingly identified among familial cancers. As such, several genes such as PALB2 are reclassified as cancer predisposition genes. But, evidence for cancer risks remains unclear for many others. In this review, we will discuss the cancer predispositions and treatment implications beyond BRCA1/BRCA2, with a focus on 24 HR genes: 53BP1, ATM,

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“…lung cancer cell line contributed to increased doxorubicin (Dox) sensitivity of the cells, on the other hand decreased Dox-induced P53 expression. According to the obtained result, it can be hypothesized that TOPBP1-dependant P53 induction by Dox leads to drug resistance (47).…”

Section: Accepted Manuscriptmentioning

confidence: 84%

Overcoming multiple drug resistance in lung cancer using siRNA targeted therapy

Naghizadeh

Mohammadi

Baradaran

et al. 2019

Gene

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Among cancers, lung cancer is the most morbidity and mortality disease that is remaining the fatalist. Generally, there are multiple treatment procedures for lung cancer, such as surgery, immunotherapy, radiotherapy and chemotherapy. There is, therefore, an urgent need for more specified and efficient methods for treatment of lung cancer such as RNAi, which in combination with traditional therapies could silence genes that are involved in the drug resistance. These genes may either be motivators of apoptosis inhibition, EMT and DNA repair system promoters or a member of intracellular signaling pathways, such as JAK/STAT, RAS/RAF/MEK, PI3K/AKT, NICD, B-catenin/TCF/LEF and their stimulator receptors including IGFR, EGFR, FGFR, VEGFR, CXCR4, MET, INTEGRINS, NOTCH1 and FRIZZLED, so could be considered as appropriate targets. In current review, the results of multiple studies which have employed drug application after one specific gene silencing or more than one gene from distinct pathways also simultaneous drug and RNAi usage in vitro and in vivo in lung cancer were summarized.

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TopBP1 contributes to the chemoresistance in non-small cell lung cancer through upregulation of p53

Cited by 15 publications

References 33 publications

ERβ Sensitizes NSCLC to Chemotherapy by Regulating DNA Damage Response

ERβ Sensitizes NSCLC to Chemotherapy by Regulating DNA Damage Response

Homologous Recombination Deficiency: Cancer Predispositions and Treatment Implications

Overcoming multiple drug resistance in lung cancer using siRNA targeted therapy

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