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| Status |
Public on Feb 05, 2022 |
| Title |
RBCK1 is an Endogenous Inhibitor for Triple Negative Breast Cancer via Hippo/YAP axis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Triple 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 identify novel therapeutic targets for TNBC. Recent genomic studies implicated the hyper-activation of Hippo/YAP signaling in TNBC, manifesting its critical roles 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. Interestingly, our data revealed an opposite function for RBCK1 in TNBC progression. RBCK1 over-expression inhibited TNBC cell progression in vitro and in vivo, while RBCK1depletion 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 showed that RBCK1 could associate with YAP protein and enhance YAP protein stability via promoting YAP K48-linked poly-ubiquitination at several YAP lysine sites (K76, K204 and K321). Our study revealed the multi-faced RBCK1 function in different subtypes of breast cancer patients and a promising therapeutic target for TNBC treatment.
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| Overall design |
Breast cancer cell mRNA samples were summarized in six samples, divided into two groups, siControl and siRBCK1
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| Contributor(s) |
Zhuang T, Li Z, Zhu J, Zhuo S |
| Citation(s) |
36280829 |
| Submission date |
Jan 29, 2022 |
| Last update date |
Nov 02, 2022 |
| Contact name |
Zhongbo li |
| E-mail(s) |
a735396587@gmail.com
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| Phone |
17796793215
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| Organization name |
Xinxiang medical university
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| Street address |
jinsuidadao601
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| City |
Xinxiang |
| State/province |
Henan |
| ZIP/Postal code |
473003 |
| Country |
China |
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| Platforms (1) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA801877 |
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