MLN4924 suppresses the BRCA1 complex and synergizes with PARP inhibition in NSCLC cells

Guo, Zongpei; Hu, Yingchun; Xie, Yu; Jin, Feng; Song, Zhi-Quan; Liu, Xiaodan; Ma, Teng; Zhou, Pingkun

doi:10.1016/j.bbrc.2016.12.162

Cited by 11 publications

(8 citation statements)

References 42 publications

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“…Apart from the induction of re-replication and DNA damage (Swords et al, 2010;Zhang et al, 2015b;Guo et al, 2017;Tong et al, 2017;Zheng et al, 2017b), a plethora of diverse mechanisms have been reported to mediate the antitumor effects of pevonedistat. These include the inhibition of the NF-kB pathway (Milhollen et al, 2010;Swords et al, 2010;Godbersen et al, 2014;Li et al, 2014a;Khalife et al, 2015); stabilization and upregulation of proapoptotic proteins such as Noxa (Dengler et al, 2014;Knorr et al, 2015;Misra et al, 2017;Wang et al, 2017); generation of ROS (Swords et al, 2010), stabilization of cell cycle regulators such as p21, p27, and WEE1 (Yang et al, 2012;Blank et al, 2013;Mackintosh et al, 2013;Huang et al, 2015;Liu et al, 2018;Wang et al, 2016); inhibition of the mammalian/mechanistic target of rapamycin (mTOR) pathway (Gu et al, 2014;Li et al, 2014a); induction of endoplasmic reticulum (ER) stress (Kuo et al, 2015;Leclerc et al, 2016); induction of immunomodulatory effects (Best et al, 2020); and activation of death receptor signaling (Chen et al, 2016a;Paiva et al, 2017).…”

Section: Melanomamentioning

confidence: 99%

“…With the multiple effects exerted by pevonedistat, it is not surprising that additive or synergistic antitumor effects are observed with mechanistically diverse antineoplastic agents including conventional cytotoxic drugs (Kee et al, 2012;Jazaeri et al, 2013;Nawrocki et al, 2013;Garcia et al, 2014;Li et al, 2014b;Ho et al, 2015;Czuczman et al, 2016;Xu et al, 2018b), radiotherapy (Wei et al, 2012;Wang et al, 2016;Xie et al, 2017;Vanderdys et al, 2018), differentiation therapy (Tan et al, 2011), and targeted therapies such as Bcl-2 inhibitors (Knorr et al, 2015), epigenetic modulators (Visconte et al, 2016;Zhou et al, 2016), monoclonal antibodies (Czuczman et al, 2016), immunomodulatory drugs (Liu et al, 2019;Zhou et al, 2019b), poly (ADPribose) polymerase inhibitors (Guo et al, 2017), BRAF inhibitors (Benamar et al, 2016), and other investigational therapies (Chen et al, 2015;Sumi et al, 2016;Cooper et al, 2017;Ishikawa et al, 2017). In certain malignancies, the cytotoxicity of pevonedistat is ameliorated by the induction of cytoprotective autophagy (Luo et al, 2012), an effect that can be overcome by combination with autophagy inhibitors leading to synergistic antitumor effects (Zhao et al, 2012;Chen et al, 2015).…”

Section: Melanomamentioning

confidence: 99%

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E1 Enzymes as Therapeutic Targets in Cancer

Barghout¹,

Schimmer²

2020

Pharmacol Rev

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Section: Melanomamentioning

confidence: 99%

Section: Melanomamentioning

confidence: 99%

E1 Enzymes as Therapeutic Targets in Cancer

Barghout¹,

Schimmer²

2020

Pharmacol Rev

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“…One proposed treatment modality for patients with NSCLC is the combination of neddylation and PARP inhibitors [ 125 ]. The neddylation E1 inhibitor, MLN4924, decreased BARD1 intensity following laser ablation.…”

Section: Bard1 In Non-breast and Non-gynecological Cancersmentioning

confidence: 99%

The Effects of Genetic and Epigenetic Alterations of BARD1 on the Development of Non-Breast and Non-Gynecological Cancers

Watters

Seltzer

MacKenzie

et al. 2020

Genes

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Breast Cancer 1 (BRCA1) gene is a well-characterized tumor suppressor gene, mutations of which are primarily found in women with breast and ovarian cancers. BRCA1-associated RING domain 1 (BARD1) gene has also been identified as an important tumor suppressor gene in breast, ovarian, and uterine cancers. Underscoring the functional significance of the BRCA1 and BARD1 interactions, prevalent mutations in the BRCA1 gene are found in its RING domain, through which it binds the RING domain of BARD1. BARD1-BRCA1 heterodimer plays a crucial role in a variety of DNA damage response (DDR) pathways, including DNA damage checkpoint and homologous recombination (HR). However, many mutations in both BARD1 and BRCA1 also exist in other domains that significantly affect their biological functions. Intriguingly, recent genome-wide studies have identified various single nucleotide polymorphisms (SNPs), genetic alterations, and epigenetic modifications in or near the BARD1 gene that manifested profound effects on tumorigenesis in a variety of non-breast and non-gynecological cancers. In this review, we will briefly discuss the molecular functions of BARD1, including its BRCA1-dependent as well as BRCA1-independent functions. We will then focus on evaluating the common BARD1 related SNPs as well as genetic and epigenetic changes that occur in the non-BRCA1-dominant cancers, including neuroblastoma, lung, and gastrointestinal cancers. Furthermore, the pro- and anti-tumorigenic functions of different SNPs and BARD1 variants will also be discussed.

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“…This was somewhat different from the findings of the present study, possibly due to the joint action of ERCC1 and other genes related to DNA damage repair. BRCA1 expression is also considered a predictive biomarker for the sensitivity of platinum drugs and is associated with the expression of PARP in NSCLC (32,33). Further studies need to be performed to explore the combined effects of different genes related to DNA damage repair on the sensitivity/resistance of platinum drugs.…”

Section: Discussionmentioning

confidence: 99%

Synergistic effects of olaparib combined with ERCC1 on the sensitivity of cisplatin in non‑small cell lung cancer

Xie

et al. 2021

Oncol Lett

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Non-small cell lung cancer (NSCLC) is a common malignant tumor. ERCC excision repair 1 endonuclease non-catalytic subunit (ERCC1) is a key mediator of nucleotide excision repair. The present study aimed to explore the synergistic effects of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib combined with ERCC1 on the sensitivity of NSCLC cells to cisplatin. Preliminary experiments were performed to identify the optimal concentrations of cisplatin and olaparib for cellular treatment and subsequently NCI-H1299 and SK-MES-1 cells were treated with 20 µg/ml cisplatin combined with 50 µg/ml olaparib and 50 µg/ml cisplatin combined with 70 µg/ml olaparib, respectively. Subsequently, transfections were carried out to overexpress or knockdown the expression of ERCC1 in NSCLC cell lines, including NCI-H1299 and SK-MES-1. The transfection efficiency was evaluated using reverse transcription-quantitative PCR and western blotting. The results demonstrated that cells with ERCC1 overexpression and ERCC1 knockdown were successfully constructed. Finally, the cell viability and apoptosis were determined using the Cell Counting Kit-8 and Annexin V-FITC cell apoptosis assays, respectively. In NCI-H1299 or SK-MES-1 cells treated with cisplatin combined with olaparib for 24 h, the cell viability significantly increased following ERCC1 overexpression compared with the GV230 group (P<0.05), but significantly inhibited following ERCC1 knockdown compared with the siRNA-NC group (P<0.05). However, ERCC1 overexpression or knockdown had the opposite effect on apoptosis. In conclusion, olaparib combined with ERCC1 expression may enhance the sensitivity of cisplatin in NSCLC. These findings may provide novel insight for the improvement of platinum drug sensitivity and treatment of NSCLC.

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MLN4924 suppresses the BRCA1 complex and synergizes with PARP inhibition in NSCLC cells

Cited by 11 publications

References 42 publications

E1 Enzymes as Therapeutic Targets in Cancer

E1 Enzymes as Therapeutic Targets in Cancer

The Effects of Genetic and Epigenetic Alterations of BARD1 on the Development of Non-Breast and Non-Gynecological Cancers

Synergistic effects of olaparib combined with ERCC1 on the sensitivity of cisplatin in non‑small cell lung cancer

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