Purpose: Pokemon, also known as ZBTB7A, belongs to the POZ and Krüppel (POK) family of transcription repressors and is implicated in tumor progression as a key proto-oncogene. This present study aimed at determining the mechanism by which Pokemon inhibits transforming growth factor β (TGFβ)-Smad4 pathway-dependent proliferation arrest of breast cancer cells via specificity protein 1 (SP1).
Methods: Over-expressing plasmid or small interfering RNA (siRNA) transfection was used to regulate Pokemon levels. The EdU incorporation assay, MTS assay, and clone formation were used to identify the inhibitory effect of Pokemon siRNA on cell proliferation. Quantitative real-time polymerase chain reaction assay confirmed that Pokemon deletion inhibited the expression of proliferation-associated genes. The dual-luciferase reporter assay, electrophoretic mobility shift assay, and co-immunoprecipitation assay were used to analyze binding between Pokemon, Smad4, and SP1.
Results: Pokemon deletion induced proliferation arrest of breast cancer cells and inhibited the expression of proliferation-associated genes, especially . Pokemon bound with SP1 to interdict Smad4 promoter activity. Information on clinical samples was obtained from The Cancer Genome Atlas data, in which the Pokemon mRNA levels showed a negative correlation with Smad4 levels in different subtypes of breast cancer in two independent datasets.
Conclusion: We demonstrated that Pokemon binds to SP1 to down-regulate Smad4 expression, thereby promoting proliferation of breast cancer cells. This suggests that Pokemon is a potential TGFβ-signaling participant in breast cancer progression.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438826 | PMC |
| http://dx.doi.org/10.4048/jbc.2019.22.e11 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Gene Polymorphisms in Greek Primary Breast Cancer Patients.
Front Biosci (Schol Ed)
December 2024
Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia.
Background: Breast cancer is a heterogeneous disease with distinct clinical subtypes, categorized by hormone receptor status, which exhibits different prognoses and requires personalized treatment approaches. These subtypes included luminal A and luminal B, which have different prognoses. Breast cancer development and progression involve many factors, including interferon-gamma ().
View Article and Find Full Text PDFDifferential Response to Cisplatin between Co-cultured Cells and Pure Cultured Cells Based on Single-cell RNA Sequencing of Three-dimensional-cultured Breast Cancer Cells.
Front Biosci (Landmark Ed)
November 2024
Department of Breast Surgery, The First People's Hospital of Foshan, 528100 Foshan, Guangdong, China.
Objective: The current study aimed to develop an experimental approach for the direct co-culture of three-dimensional breast cancer cells using single-cell RNA sequencing (scRNA-seq).
Methods: The following four cell culture groups were established in the Matrigel matrix: the untreated Michigan Cancer Foundation (MCF)-7 cell culture group, the MCF-7 cell culture plus cisplatin group, the untreated co-culture group, and the cell co-culture plus cisplatin group. For cell co-culture, MCF-7 cells, human mammary fibroblasts, and human umbilical vein endothelial cells were mixed at a ratio of 1:1:1.
Clinical Relevance and Drug Modulation of PPAR Signaling Pathway in Triple-Negative Breast Cancer: A Comprehensive Analysis.
PPAR Res
December 2024
Department of Laboratory Medicine, The Sixth School of Clinical Medicine, The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, China.
Triple-negative breast cancer (TNBC) is highly heterogeneous and poses a significant medical challenge due to limited treatment options and poor outcomes. Peroxisome proliferator-activated receptors (PPARs) play a crucial role in regulating metabolism and cell fate. While the association between PPAR signal and human cancers has been a topic of concern, its specific relationship with TNBC remains unclear.
View Article and Find Full Text PDFEffectiveness of a Breast Cancer Educational Conference Targeting Healthcare Workers in Honduras.
Int J Breast Cancer
December 2024
Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
Previous studies have demonstrated that many healthcare workers in low- and middle-income countries (LMICs) lack the appropriate training and knowledge to recognize and diagnose breast cancer at an early stage. As a result, women in LMICs are frequently diagnosed with late-stage breast cancer (Stage III/IV) with a poor prognosis. We hosted a 1-day breast cancer educational conference directed towards healthcare workers in Honduras.
View Article and Find Full Text PDFDeep learning identification of novel autophagic protein-protein interactions and experimental validation of Beclin 2-Ubiquilin 1 axis in triple-negative breast cancer.
Oncol Res
December 2024
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Background: Triple-negative breast cancer (TNBC), characterized by its lack of traditional hormone receptors and HER2, presents a significant challenge in oncology due to its poor response to conventional therapies. Autophagy is an important process for maintaining cellular homeostasis, and there are currently autophagy biomarkers that play an effective role in the clinical treatment of tumors. In contrast to targeting protein activity, intervention with protein-protein interaction (PPI) can avoid unrelated crosstalk and regulate the autophagy process with minimal interference pathways.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!