TGF-β signaling is a therapeutic target in advanced cancers. We identified tumor necrosis factor receptor-associated factor 4 (TRAF4) as a key component mediating pro-oncogenic TGF-β-induced SMAD and non-SMAD signaling. Upon TGF-β stimulation, TRAF4 is recruited to the active TGF-β receptor complex, where it antagonizes E3 ligase SMURF2 and facilitates the recruitment of deubiquitinase USP15 to the TGF-β type I receptor (TβRI). Both processes contribute to TβRI stabilization on the plasma membrane and thereby enhance TGF-β signaling. In addition, the TGF-β receptor-TRAF4 interaction triggers Lys 63-linked TRAF4 polyubiquitylation and subsequent activation of the TGF-β-activated kinase (TAK)1. TRAF4 is required for efficient TGF-β-induced migration, epithelial-to-mesenchymal transition, and breast cancer metastasis. Elevated TRAF4 expression correlated with increased levels of phosphorylated SMAD2 and phosphorylated TAK1 as well as poor prognosis among breast cancer patients. Our results demonstrate that TRAF4 can regulate the TGF-β pathway and is a key determinant in breast cancer pathogenesis.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.molcel.2013.07.014 | DOI Listing |
Cell Mol Biol Lett
January 2025
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata Di Rende, 87036, Cosenza, Italy.
Breast cancer is the most commonly diagnosed type of cancer and the leading cause of cancer-related death in women worldwide. Highly targeted therapies have been developed for different subtypes of breast cancer, including hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, triple-negative breast cancer (TNBC) and metastatic breast cancer disease are primarily treated with chemotherapy, which improves disease-free and overall survival, but does not offer a curative solution for these aggressive forms of breast cancer.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Genetics, The University of Alabama at Birmingham, Birmingham, AL, USA.
Nowadays, chemotherapy and immunotherapy remain the major treatment strategies for Triple-Negative Breast Cancer (TNBC). Identifying biomarkers to pre-select and subclassify TNBC patients with distinct chemotherapy responses is essential. In the current study, we performed an unbiased Reverse Phase Protein Array (RPPA) on TNBC cells treated with chemotherapy compounds and found a leading significant increase of phosphor-AURKA/B/C, AURKA, AURKB, and PLK1, which fall into the mitotic kinase group.
View Article and Find Full Text PDFSci Rep
January 2025
Chair of Obstetrics Development, Faculty of Health Sciences, Medical University of Lublin, Lublin, Poland.
The aim of the study is to analyze the relationship between personality traits of women with hereditary predisposition to breast/ovarian cancer and their obstetric history and cancer-preventive behaviors. A total of 357 women, participants of 'The National Program for Families With Genetic/Familial High Risk for Cancer', were included in the study. The Neo Five-Factor Inventory (NEO-FFI) and a standardized original questionnaire designed for the purpose of the study were used.
View Article and Find Full Text PDFSci Rep
January 2025
College of Information Science and Technology, Hainan Normal University, Haikou, 571158, China.
Breast cancer is one of the most aggressive types of cancer, and its early diagnosis is crucial for reducing mortality rates and ensuring timely treatment. Computer-aided diagnosis systems provide automated mammography image processing, interpretation, and grading. However, since the currently existing methods suffer from such issues as overfitting, lack of adaptability, and dependence on massive annotated datasets, the present work introduces a hybrid approach to enhance breast cancer classification accuracy.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Thyroid and Breast Surgery, Liaoning Provincial People's Hospital, People's Hospital of China Medical University), Shenyang, China.
This study aimed to explore the diagnostic value of the two cytology techniques, including liquid-based cytology of mammary ductal lavage fluid and nipple discharge smear cytology, in the intraductal lesions in patients with pathological nipple discharge (PND). This retrospective analysis included 119 patients with PND who underwent surgical treatment. At the same time, they all underwent fiberoptic ductoscopy (FDS), nipple discharge smear cytology and liquid-based cytology of ductal lavage fluid before surgery.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!