scholarly journals Inhibition of triple‑negative breast cancer proliferation and motility by reactivating p53 and inhibiting overactivated Akt

2021 ◽  
Vol 47 (2) ◽  
Author(s):  
Wei Cao ◽  
Renhui Shen ◽  
Seth Richard ◽  
Yu Liu ◽  
Mohammad Jalalirad ◽  
...  
2022 ◽  
Author(s):  
Zhi Li ◽  
Hai-Yan Yang ◽  
Xiao-Lan Zhang ◽  
Xu Zhang ◽  
Yu-Zhou Huang ◽  
...  

Abstract Background: Triple negative breast cancer (TNBC) is highly malignant and has a worse prognosis, compared with other subtypes of breast cancer due to the absence of therapeutic targets. MKLP1 plays a crucial role in tumorigenesis and cancer progression. However, the role of MKLP1 in triple negative breast cancer and the underlying mechanism remain unknown. The study aimed to elucidate the biological function regulatory mechanism of MKLP1 in triple negative breast cancerMethods: Quantitative real-time PCR and Western blotting were used to determine the MKLP1 expression in breast cancer tissues and cell lines. Then, functional experiments in vitro and in vivo were performed to investigate the effects of MKLP1 on tumor growth and metastasis in triple negative breast cancer. Chromatin immunoprecipitation assay was conducted to illustrate the potential regulatory mechanisms of MKLP1 in triple negative breast cancer.Results: We found that MKLP1 was significantly up-regulated and associated with poor prognosis in triple negative breast cancer. MKLP1 could promote triple negative breast cancer proliferation, migration and invasion in vitro and in vivo. MKLP1 could activate Wnt/β-catenin pathway and promote EMT progression. In addition, FOXM1, upregulated by WDR5 via H3K4me3 modification, directly bound to the promoter of MKLP1 gene to promote its transcription and accelerated TNBC progression via Wnt/β-catenin pathway. Both of small inhibitor of FOXM1 and WDR5 could inhibit TNBC progression. Conclusions: Our findings elucidate WDR5/FOXM1/MKLP1/Wnt/β-catenin axis is associated with TNBC progression and may provide a novel and promising therapeutic target for TNBC treatment.


2020 ◽  
Vol Volume 12 ◽  
pp. 6241-6249
Author(s):  
Ruizhen Wu ◽  
Bingqing Zhao ◽  
Xunxin Ren ◽  
Shiheng Wu ◽  
Mingzao Liu ◽  
...  

2011 ◽  
Author(s):  
Lixin Yang ◽  
Xiwei Wu ◽  
Xutao Deng ◽  
Sean Lau ◽  
George Somlo ◽  
...  

Author(s):  
Fu Peng ◽  
Hailin Tang ◽  
Junrong Du ◽  
Jianping Chen ◽  
Cheng Peng

Triple-negative breast cancer (TNBC) is the subtype of breast cancer with more aggressive growth and metastasis and without efficient therapies. Hence, it is worthwhile to search for potential effective drug candidates. According to our previous study, isoliquiritigenin (ISL) exerted a potent anticancer effect on breast cancer proliferation. Its effect on TNBC growth, metastasis and mechanism deserves further investigation. In this study, PCR array screened a significant increase of miR-200c in BT-549 and MDA-MB-231 cells after ISL treatment, and ISH exerted that miR-200c was expressed at a low level in breast cancer tissue of patients. We also found that ISL could up-regulate miR-200c, resulting in the inhibition of epithelial-mesenchymal transition. Meanwhile, ISL could inhibit metastasis and tumor growth in nude mice models through the increase of miR-200c. Further study displayed that ISL decreased c-Jun expression through the increase of miR-200c. Interestingly, we also detected that ISL might increase miR-200c expression through the demethylation of miR-200c promoter region. These findings indicated that ISL could be potentially developed as a novel drug candidate for TNBC in microRNA-based cancer therapies.


Planta Medica ◽  
2015 ◽  
Vol 81 (11) ◽  
Author(s):  
AJ Robles ◽  
L Du ◽  
S Cai ◽  
RH Cichewicz ◽  
SL Mooberry

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