The ubiquitin ligase CUL4A has been implicated in tumorigenesis, but its contributions to progression and metastasis have not been evaluated. Here, we show that CUL4A is elevated in breast cancer as well as in ovarian, gastric, and colorectal tumors in which its expression level correlates positively with distant metastasis. CUL4A overexpression in normal or malignant human mammary epithelial cells increased their neoplastic properties in vitro and in vivo, markedly increasing epithelial-mesenchymal transition (EMT) and the metastatic capacity of malignant cells. In contrast, silencing CUL4A in aggressive breast cancer cells inhibited these processes. Mechanistically, we found that CUL4A modulated histone H3K4me3 at the promoter of the EMT regulatory gene ZEB1 in a manner associated with its transcription. ZEB1 silencing blocked CUL4A-driven proliferation, EMT, tumorigenesis, and metastasis. Furthermore, in human breast cancers, ZEB1 expression correlated positively with CUL4A expression and distant metastasis. Taken together, our findings reveal a pivotal role of CUL4A in regulating the metastatic behavior of breast cancer cells.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934357 | PMC |
| http://dx.doi.org/10.1158/0008-5472.CAN-13-2182 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
In Vitro Cytotoxic Potential and Integrated Network Pharmacology, Molecular Docking and Molecular Dynamic Approaches to Decipher the Mechanism of Gymnostachyum febrifugum Benth., in the Treatment of Breast Cancer.
Appl Biochem Biotechnol
January 2025
Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, 575018, Karnataka, India.
Gymnostachyum febrifugum, a less-known ethnomedicinal plant from the Western Ghats of India, is used to treat various diseases and serves as an antioxidant and antibacterial herb. The present study aims to profile the cytotoxic phytochemicals in G. febrifugum roots using GC-MS/MS, in vitro confirmation of cytotoxic potential against breast cancer and an in silico study to understand the mechanism of action.
View Article and Find Full Text PDFBreast density assessment via quantitative sound-speed measurement using conventional ultrasound transducers.
Eur Radiol
January 2025
Department of Information Technology, Uppsala University, 75237, Uppsala, Sweden.
Objectives: The aim is to assess the feasibility and accuracy of a novel quantitative ultrasound (US) method based on global speed-of-sound (g-SoS) measurement using conventional US machines, for breast density assessment in comparison to mammographic ACR (m-ACR) categories.
Materials And Methods: In a prospective study, g-SoS was assessed in the upper-outer breast quadrant of 100 women, with 92 of them also having m-ACR assessed by two radiologists across the entire breast. For g-SoS, ultrasonic waves were transmitted from varying transducer locations and the image misalignments between these were then related analytically to breast SoS.
Unraveling the potential mechanism and prognostic value of pentose phosphate pathway in hepatocellular carcinoma: a comprehensive analysis integrating bulk transcriptomics and single-cell sequencing data.
Funct Integr Genomics
January 2025
Institute of Infectious Diseases, Guangdong Province, Guangzhou Eighth People's Hospital, Guangzhou Medical University, 8 Huaying Road, Baiyun District, Guangzhou, 510440, China.
Hepatocellular carcinoma (HCC) remains a malignant and life-threatening tumor with an extremely poor prognosis, posing a significant global health challenge. Despite the continuous emergence of novel therapeutic agents, patients exhibit substantial heterogeneity in their responses to anti-tumor drugs and overall prognosis. The pentose phosphate pathway (PPP) is highly activated in various tumor cells and plays a pivotal role in tumor metabolic reprogramming.
View Article and Find Full Text PDFKnockdown of miR-182 changes the sensitivity of triple-negative breast cancer cells to cisplatin.
Nucleosides Nucleotides Nucleic Acids
January 2025
Division of Hematology, Department of Internal Medicine, Medical Faculty, Tekirdağ Namık Kemal University, Tekirdağ, Turkey.
Breast cancer is the most common malignancy that affects women. MicroRNAs (miRNAs) play an essential role in cancer therapy and regulate many biological processes such as cisplatin resistance. The study's objective was to determine whether miR-182 dysregulation was the cause of cisplatin resistance in TNBC cell line MDA-MB-231.
View Article and Find Full Text PDFTP53 mutations and MDM2 polymorphisms in breast and ovarian cancers: amelioration by drugs and natural compounds.
Clin Transl Oncol
January 2025
Inflammation and Cancer Biology Laboratory, Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur, Assam, 784028, India.
Globally, breast and ovarian cancers are major health concerns in women and account for significantly high cancer-related mortality rates. Dysregulations and mutations in genes like TP53, BRCA1/2, KRAS and PTEN increase susceptibility towards cancer. Here, we discuss the impact of mutations in the key regulatory gene, TP53 and polymorphisms in its negative regulator MDM2 which are reported to accelerate cancer progression.
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!