Deregulation of E3 ubiquitin ligases is intimately implicated in breast cancer pathogenesis and progression, but the underlying mechanisms still remain elusive. Here we report that RING finger protein 144A (RNF144A), a poorly characterized member of the RING-in-between-RING family of E3 ubiquitin ligases, functions as a tumor suppressor in breast cancer. RNF144A was downregulated in a subset of primary breast tumors and restoration of RNF144A suppressed breast cancer cell proliferation, colony formation, migration, invasion in vitro, tumor growth, and lung metastasis in vivo. In contrast, knockdown of RNF144A promoted malignant phenotypes of breast cancer cells. Quantitative proteomics and biochemical analysis revealed that RNF144A interacted with and targeted heat-shock protein family A member 2 (HSPA2), a putative oncoprotein that is frequently upregulated in human cancer and promotes tumor growth and progression, for ubiquitination and degradation. Notably, the ligase activity-defective mutants of RNF144A impaired its ability to induce ubiquitination and degradation of HSPA2, and to suppress breast cancer cell proliferation, migration, and invasion as compared with its wild-type counterpart. Moreover, RNF144A-mediated suppression of breast cancer cell proliferation, migration, and invasion was rescued by ectopic HSPA2 expression. Clinically, low RNF144A and high HSPA2 expression in breast cancer patients was correlated with aggressive clinicopathological characteristics and decreased overall and disease-free survival. Collectively, these findings reveal a previously unappreciated role for RNF144A in suppression of breast cancer growth and metastasis, and identify RNF144A as the first, to our knowledge, E3 ubiquitin ligase for HSPA2 in human cancer.
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http://dx.doi.org/10.1038/s41418-019-0400-z | DOI Listing |
ACS Sens
December 2024
School of Mechanical Engineering, Southeast University, Nanjing 211189, People's Republic of China.
Background noise interferes with the accurate detection of early tumor biomarkers. This study introduces a method that effectively reduces background noise to enhance detection accuracy by combining a color-coded signaling approach with the unique fluorescent properties and room-temperature tunable quantum spin characteristics of fluorescent diamonds (FNDs) with nitrogen-vacancy centers. In this approach, a red signal indicates the presence of the target analyte within the spectral region, a green signal indicates its absence, and a yellow signal indicates the need for further analysis using FNDs' quantum spin properties for optical detection magnetic resonance (ODMR) to distinguish the FND signal from background noise.
View Article and Find Full Text PDFChempluschem
December 2024
Centre for Inorganic Chemistry, Chemistry, Bv 120, e/ 60 y 64, Nº1465, 1900, La Plata, ARGENTINA.
The redox imbalance, caused by depletion or generation of reactive oxygen species (ROS), is a key mechanism by which metal complexes exert anticancer effects. Carbidopa has shown the ability to inhibit the MDA-MB-231 cell line, a highly aggressive triple-negative human breast adenocarcinoma, by inducing reductive stress. The metal complex of carbidopa with zinc (ZnCarbi) was designed to modify carbidopa's structure and exhibited increased cytotoxicity against MDA-MB-231 cells.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
December 2024
Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350000, P.R. China.
Ubiquitin‑specific protease 35 (USP35) was found to be involved in various tumor progression, but its role in breast cancer remains largely unknown. USP35 mRNA and protein expression in breast cancer tissues and cells were evaluated by qPCR and Western bolt (WB), respectively. Subsequently, flow cytometry and EDU labeling were used to evaluate breast cancer cell apoptosis and proliferation.
View Article and Find Full Text PDFCardiol Ther
December 2024
Cardio-Oncology Program, Division of Cardiovascular Medicine, Department of Medicine, Lahey Hospital and Medical Center, 41 Mall Road, Burlington, MA, 01805, USA.
In addition to traditional risk factors, patients with breast cancer are at an increased risk of atrial fibrillation due to cancer itself and certain cancer therapies. Atrial fibrillation in these patients adds to their morbidity and mortality. The precise mechanisms leading to the increased atrial fibrillation in patients with breast cancer are not well understood.
View Article and Find Full Text PDFBiometals
December 2024
Department of Chemistry, Baba Mastnath University, Asthal Bohar, Rohtak, 124021, India.
The Schiff base metal complexes containing the transition metal ions Co(II), Ni(II) and Cu(II) were synthesized using their nitrate and acetate salts. An octahedral environment encircling metal complexes has been demonstrated by the findings of multiple spectroscopic approaches that were employed to demonstrate the structure of the metal complexes. The Coats-Redfern method of thermal analysis was employed to carry out the kinetic and thermodynamic calculations.
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