Discovery of novel mifepristone derivatives via suppressing KLF5 expression for the treatment of triple-negative breast cancer

Lin, Yuqi; Liu, Rong; Zhao, Ping; Ye, Jinxiang; Zhang, Zheng; Huang, Jingan; Zhang, Yingying; Gao, Yu; Chen, Haiying; Liu, Suling; Zhou, Jia; Chen, Ceshi; Chen, Haijun

doi:10.1016/j.ejmech.2018.01.056

Cited by 16 publications

(9 citation statements)

References 43 publications

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“…Publications have proven that KLF5 plays an important role in many malignant tumors, such as bladder cancer [24], prostate cancer [25], breast cancer [26], colon cancer, thyroid cancer [27], etc., but the biological behavior of KLF5 is different in different tumors [28]. Nandan et al [29] found that KLF5 was highly expressed in the proliferative and active crypt epithelium of normal intestinal tissues.…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of Lysophosphatidic Acid Receptor-2 (LPA2) and Krüppel-Like Factor 5 (KLF5) Protein Expression Detected by Tissue Microarray in Gastric Adenocarcinoma

Zhu

2019

Med Sci Monit

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Background The aim of this study was to evaluate lysophosphatidic acid receptor-2 (LPA2) and Krüppel-like factor 5 (KLF5) protein expression in gastric adenocarcinoma and their correlation with patient clinicopathological characteristics and prognosis. Material/Methods Fifty-one gastric adenocarcinoma tissue samples, 21 gastric intraepithelial neoplasia (GIN) samples, and 13 normal gastric tissue samples were collected to test for LPA2 and KLF5 expression by tissue microarray and immunohistochemistry assay. LPA2 and KLF5 positive expression rate between gastric adenocarcinoma, GIN, and normal gastric tissue were compared. The relationship between LPA2 expression, KLF5 expression, and patients’ clinicopathological characteristics and prognosis were evaluated. Results The positive expression rate of LPA2 and KLF5 were statistical different in gastric adenocarcinoma, GIN, and normal gastric tissue ( P <0.05). LPA2 positive expression was associated with tumor invasion depth, Lauren type, vascular invasion, local lymph node metastasis, and clinical stage ( P <0.05). There was no correlation between LPA2 expression (hazard ratio [HR]=1.84, 95% confidence interval [CI]: 0.89–3.80, P >0.05), KLF5 expression (HR=1.13, 95% CI: 0.53–2.36, P >0.05), and gastric cancer patients’ overall survival. Conclusions LPA2 and KLF5 protein expressions were differently expressed in gastric adenocarcinoma, GIN, and normal gastric tissue, and differences were correlated with patients’ clinical characteristic. However, LPA2 and KLF5 expressions were not correlated with the patients’ prognosis.

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Section: Discussionmentioning

confidence: 99%

Clinical Significance of Lysophosphatidic Acid Receptor-2 (LPA2) and Krüppel-Like Factor 5 (KLF5) Protein Expression Detected by Tissue Microarray in Gastric Adenocarcinoma

Zhu

2019

Med Sci Monit

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“…75 Two mifepristone-derived compounds, FZU-00,003 and FZU-00,004, showed higher efficiency. 158,159 Second, metformin suppressed PKA activity, promoted GSK3β-mediated KLF5 phosphorylation and degradation and decreased TNBC stem cells. 6 Additionally, mithramycin A inhibited TNBC by inhibiting the binding of Sp1 to the KLF5 promoter and the binding of KLF5 to the FGF-BP1 promoter.…”

Section: Targ E Ted Ther Apymentioning

confidence: 99%

The roles and regulation of the KLF5 transcription factor in cancers

Luo

Chen

2021

Cancer Science

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“…In short, KLF4 plays a pivotal role in promoting CSCs formation and has been used as a CSC marker. Other members of the KLFs family are also associated with the mediation of CSCs, such as KLF5 84–86 . Overexpression of KLF5 results in the enrichment of the CD44 High /CD133 High subpopulation and increase the capacity of drug resistance and colony formation in CSCs of hepatocellular carcinoma (HCC) 87 .…”

Section: The Pivotal Roles Of Transcriptional Regulation In Cancer De...mentioning

confidence: 99%

“…Other members of the KLFs family are also associated with the mediation of CSCs, such as KLF5. [84][85][86] Overexpression of KLF5 results in the enrichment of the CD44 High /CD133 High subpopulation and increase the capacity of drug resistance and colony formation in CSCs of hepatocellular carcinoma (HCC). 87 In addition, some other TFs have been identified as drivers of the leukemia stem cell population, such as MLL-AF9 and CBFβ-SMMHC.…”

Section: Cancer Stem Cells (Cscs)mentioning

confidence: 99%

Targeting key proteins involved in transcriptional regulation for cancer therapy: Current strategies and future prospective

Pei

Guo

Peng

et al. 2022

Medicinal Research Reviews

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The key proteins involved in transcriptional regulation play convergent roles in cellular homeostasis, and their dysfunction mediates aberrant gene expressions that underline the hallmarks of tumorigenesis. As tumor progression is dependent on such abnormal regulation of transcription, it is important to discover novel chemical entities as antitumor drugs that target key tumor‐associated proteins involved in transcriptional regulation. Despite most key proteins (especially transcription factors) involved in transcriptional regulation are historically recognized as undruggable targets, multiple targeting approaches at diverse levels of transcriptional regulation, such as epigenetic intervention, inhibition of DNA‐binding of transcriptional factors, and inhibition of the protein–protein interactions (PPIs), have been established in preclinically or clinically studies. In addition, several new approaches have recently been described, such as targeting proteasomal degradation and eliciting synthetic lethality. This review will emphasize on accentuating these developing therapeutic approaches and provide a thorough conspectus of the drug development to target key proteins involved in transcriptional regulation and their impact on future oncotherapy.

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Discovery of novel mifepristone derivatives via suppressing KLF5 expression for the treatment of triple-negative breast cancer

Cited by 16 publications

References 43 publications

Clinical Significance of Lysophosphatidic Acid Receptor-2 (LPA2) and Krüppel-Like Factor 5 (KLF5) Protein Expression Detected by Tissue Microarray in Gastric Adenocarcinoma

Clinical Significance of Lysophosphatidic Acid Receptor-2 (LPA2) and Krüppel-Like Factor 5 (KLF5) Protein Expression Detected by Tissue Microarray in Gastric Adenocarcinoma

The roles and regulation of the KLF5 transcription factor in cancers

Targeting key proteins involved in transcriptional regulation for cancer therapy: Current strategies and future prospective

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