ArticleCell communication and signaling : CCS2022
RBCK1 is an endogenous inhibitor for triple negative breast cancer via hippo/YAP axis.
Article in Cell communication and signaling : CCS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 16 citations in OpenAlex.
- SETD8-mediated mono-methylation of YAP at K76 promotes K48-linked polyubiquitination and degradation to suppress colorectal cancer.Cell death and differentiation · 2026Article
- OTUD4 regulates pancreatic cancer progression via Hippo/YAP axis.Neoplasia (New York, N.Y.) · 2026Article
- NEDD4 promotes reactive astrogliosis by enhancing K63-linked ubiquitination and inhibiting chaperone-mediated autophagy degradation of YAP1.International journal of biological sciences · 2026Article
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- Clinically friendly smart hydrogel boosts cuproptosis and PD-L1 upregulation to enhance anti-tumor immunotherapy.Materials today. Bio · 2025Article
- Posttranslational modifications of YAP/TAZ: molecular mechanisms and therapeutic opportunities.Cellular & molecular biology letters · 2025Review
- LINC00525 drives aggressive phenotypes in bladder cancer via YAP stabilization-mediated transcriptional activation.Cancer cell international · 2025Article
- USP12 facilitates gastric cancer progression via stabilizing YAP.Cell death discovery · 2024Article
- Article
- Mechanisms underlying linear ubiquitination and implications in tumorigenesis and drug discovery.Cell communication and signaling : CCS · 2023Review
- Regulation of the Hippo/YAP axis by CXCR7 in the tumorigenesis of gastric cancer.Journal of experimental & clinical cancer research : CR · 2023Article
- PANoptosis-related prognostic signature predicts overall survival of cutaneous melanoma and provides insights into immune infiltration landscape.Scientific reports · 2023Article
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Authors and funding
15 authors at 5 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundTriple negative breast cancer (TNBC) is one of the most lethal breast cancer subtypes. Due to a lack of effective therapeutic targets, chemotherapy is still the main medical treatment for TNBC patients. Thus, it is important and necessary to find new therapeutic targets for TNBC. Recent genomic studies implicated the Hippo / Yap signal is over activated in TNBC, manifesting it plays a key role in TNBC carcinogenesis and cancer progression. RBCK1 was firstly identified as an important component for linear ubiquitin assembly complex (LUBAC) and facilitates NFKB signaling in immune response. Further studies showed RBCK1 also facilitated luminal type breast cancer growth and endocrine resistance via trans-activation estrogen receptor alpha.
methodsRBCK1 and YAP protein expression levels were measured by western blotting, while the mRNA levels of YAP target genes were measured by RT-PCR. RNA sequencing data were analyzed by Ingenuity Pathway Analysis. Identification of Hippo signaling activity was accomplished with luciferase assays, RT-PCR and western blotting. Protein stability assays and ubiquitin assays were used to detect YAP protein degradation. Ubiquitin-based immunoprecipitation assays were used to detect the specific ubiquitination modification on the YAP protein.
resultsIn our current study, our data revealed an opposite function for RBCK1 in TNBC progression. RBCK1 over-expression inhibited TNBC cell progression in vitro and in vivo, while RBCK1 depletion promoted TNBC cell invasion. The whole genomic expression profiling showed that RBCK1 depletion activated Hippo/YAP axis. RBCK1 depletion increased YAP protein level and Hippo target gene expression in TNBC. The molecular biology studies confirmed that RBCK1 could bind to YAP protein and enhance the stability of YAP protein by promoting YAP K48-linked poly-ubiquitination at several YAP lysine sites (K76, K204 and K321).
conclusionOur study revealed the multi-faced RBCK1 function in different subtypes of breast cancer patients and a promising therapeutic target for TNBC treatment. Video abstract.
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