Inhibition of the CDK9–cyclin T1 protein–protein interaction as a new approach against triple-negative breast cancer

Cheng, Shasha; Qu, Yuan Qing; Wu, Jia; Yang, Guan–Jun; Líu, Hao; Wang, Wanhe; Huang, Qi; Chen, Feng; Li, Guodong; Wong, Chun‐Yuen; Wong, Vincent Kam Wai; Leung, Chung‐Hang

doi:10.1016/j.apsb.2021.10.024

Cited by 42 publications

(28 citation statements)

References 64 publications

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“…Wnt/β-catenin also serves as a common upstream signal for EMT, and an aberrant Wnt signaling in NSCLC, which often induces cellular EMT [ 41 ]. Interestingly, emerging investigations have designed some low-toxicity small-molecule drugs targeting less highly conserved regions of the proteins to disrupt protein-protein interactions (PPI), which was effective in reversing EMT in breast cancer cells, showing a surprising inhibition of tumor growth and distant metastasis [ 42 , 43 ]. Hence, disrupting PPI associated with Wnt signaling and EMT in NSCLC may be a promising strategy to explore.…”

Section: Discussionmentioning

confidence: 99%

LINC00514 facilitates cell proliferation, migration, invasion, and epithelial-mesenchymal transition in non-small cell lung cancer by acting on the Wnt/β-catenin signaling pathway

Zhu

Yang

et al. 2022

Bioengineered

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The long non-coding RNA (lncRNA) LINC00514 was identified to play an essential oncogenic function in different human cancers, but its effects in non-small cell lung cancer (NSCLC) are yet to be elucidated. In this study, we evaluated the function of LINC00514 in NSCLC. LINC00514 expression and prognosis in NSCLC were analyzed using qRT-PCR and online bioinformatic tools. The bioeffects of LINC0514 in NSCLC cells were examined using cell counting kit-8, colony formation, and transwell assays. Western blotting was used to measure the expression of the target proteins. The LINC00514 regulation of the Wnt/β-catenin signaling pathway was assessed using a specific agonist (LiCl) and luciferase reporter assay. We found that LINC00514 expression was elevated in NSCLC cells and clinical samples and that increased LINC00514 expression predicted poorer patient prognosis. Silencing LINC00514 suppresses proliferation, migration, and invasion of NSCLC cells. Downregulation of LINC00514 inhibited Wnt/β-catenin signaling and epithelial-mesenchymal transition (EMT). Moreover, suppression of the biological phenotypes of NSCLC cells induced by LINC00514 gene silencing was restored after LiCl treatment. Finally, we found that silencing LINC00514 attenuated the growth of xenograft tumors in vivo. Altogether, this study provides the latest convincing evidence that LINC00514 facilitates the malignant biological behavior of NSCLC cells through activation of the Wnt/β-catenin pathway, which might offer a beneficial approach for the treatment of NSCLC.

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Section: Discussionmentioning

confidence: 99%

LINC00514 facilitates cell proliferation, migration, invasion, and epithelial-mesenchymal transition in non-small cell lung cancer by acting on the Wnt/β-catenin signaling pathway

Zhu

Yang

et al. 2022

Bioengineered

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“…Screening for possible activities was conducted to select the compounds that have function to interact with pathway signaling in the cells using the PASS Online web server ( https://www.way2drug.com/passonline/ ). The pathway activity was selected based on their functions as anti-breast cancer agents such as MMP9 expression inhibitor [ 28 ], apoptosis agonist [ 29 ], JAK2 expression inhibitor [ 30 ], antineoplastic (breast cancer) [ 31 ] and proliferative disease treatment agent [ 32 ], caspase-3 stimulant [ 33 ], caspase-8 stimulant [ 33 ], topoisomerase I inhibitor [ 34 ], topoisomerase II inhibitor [ 34 ], cancer-associated disorder treatment agent [ 35 ], protein kinase C inhibitor [ 36 ], CDC25 phosphatase inhibitor [ 37 ], and CDK9/cyclin T1 inhibitor [ 38 ].…”

Section: Methodsmentioning

confidence: 99%

A Potential Anticancer Mechanism of Finger Root (Boesenbergia rotunda) Extracts against a Breast Cancer Cell Line

et al. 2022

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Breast cancer is the most common type of cancer women suffer from worldwide in 2020 and the 4th leading cause of cancer death. Boesenbergia rotunda is an herb with high potential as an anticancer agent. This study explores the potential bioactive compounds in B. rotunda as anti-breast cancer agents using in silico and in vitro approaches. The in silico study was used for active compound analysis, selection of anticancer compound candidates, prediction of target protein, functional annotation, molecular docking, and molecular dynamics simulation, respectively. The in vitro study was conducted by measurement toxicity, rhodamine 123, and apoptosis assays on T47D cells. Based on the KNApSAcK database, B. rotunda contained 20 metabolites, which are dominated by chalcone and flavonoid groups. Seven of them were predicted to have anticancer activity, namely, sakuranetin, cardamonin, alpinetin, 2S-pinocembrin, 7.4′-dihydroxy-5-methoxyflavanone, 5.6-dehydrokawain, and pinostrobin chalcone. These compounds targeted proteins related to cancer progression pathways such as the PI3K/Akt, FOXO, JAK/STAT, and estrogen signaling pathways. Therefore, these compounds are predicted to inhibit growth and induce apoptosis of cancer cells through their interactions with MMP12, MMP13, CDK4, JAK3, VEGFR1, VEGFR2, and KCNA3. Anticancer activity of B. rotunda through in vitro study confirmed that B. rotunda extract is strong cytotoxic and induces apoptosis of breast cancer cell lines. This study concludes that Boesenbergia rotunda has potency as an anticancer candidate.

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“…But the detailed mechanisms of the LSD1 in BC progression are unclear and more potential anti-tumor pathways or downstream genes are yet to clarify due to the heterogeneity of varieties of BC subtypes. For example, metastasis and drug resistance are two main factors responsible for BCcaused death in clinic (Cheng et al, 2021;Cheng et al, 2022a). Although there are several reported researches on the roles of LSD1 in BC metastasis and drug resistance, the specific functions of LSD1 in these two cancer cell events are yet to be investigated.…”

Section: Dual-target Inhibitors and Combined Therapymentioning

confidence: 99%

A state-of-the-art review on LSD1 and its inhibitors in breast cancer: Molecular mechanisms and therapeutic significance

et al. 2022

Self Cite

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Breast cancer (BC) is a kind of malignant cancer in women, and it has become the most diagnosed cancer worldwide since 2020. Histone methylation is a common biological epigenetic modification mediating varieties of physiological and pathological processes. Lysine-specific demethylase 1 (LSD1), a first identified histone demethylase, mediates the removal of methyl groups from histones H3K4me1/2 and H3K9me1/2 and plays a crucial role in varieties of cancer progression. It is also specifically amplified in breast cancer and contributes to BC tumorigenesis and drug resistance via both demethylase and non-demethylase manners. This review will provide insight into the overview structure of LSD1, summarize its action mechanisms in BC, describe the therapeutic potential of LSD1 inhibitors in BC, and prospect the current opportunities and challenges of targeting LSD1 for BC therapy.

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Inhibition of the CDK9–cyclin T1 protein–protein interaction as a new approach against triple-negative breast cancer

Cited by 42 publications

References 64 publications

LINC00514 facilitates cell proliferation, migration, invasion, and epithelial-mesenchymal transition in non-small cell lung cancer by acting on the Wnt/β-catenin signaling pathway

LINC00514 facilitates cell proliferation, migration, invasion, and epithelial-mesenchymal transition in non-small cell lung cancer by acting on the Wnt/β-catenin signaling pathway

A Potential Anticancer Mechanism of Finger Root (Boesenbergia rotunda) Extracts against a Breast Cancer Cell Line

A state-of-the-art review on LSD1 and its inhibitors in breast cancer: Molecular mechanisms and therapeutic significance

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