| Literature DB >> 35122005 |
Min Cong1, Yuan Wang1, Yang Yang2, Cheng Lian1, Xueqian Zhuang1, Xiaoxun Li1, Peiyuan Zhang1, Yingjie Liu1, Jun Tang3, Qifeng Yang4, Xue Zhang1, Hua Xiong5, Ronggui Hu6, Guohong Hu7.
Abstract
Tumor-initiating cells (TICs) are considered the culprits of cancer development and progression. Dysregulation of metastasis suppressor protein 1 (MTSS1) has been widely observed in tumor metastasis, but its functional contribution and mechanism in cancer is poorly understood. Here we report a role of MTSS1 in suppressing TICs in breast cancer. Mtss1 knockout (KO) enhances the mammary epithelial TIC subpopulation in both luminal and basal-like breast cancer mouse models. MTSS1 also suppresses tumorsphere formation in breast cancer cells. Mechanistically, MTSS1 interacts with the E3 ligase RanBP2-type and C3HC4-type zinc finger containing 1 (RBCK1) to facilitate RBCK1-mediated p65 ubiquitination and degradation, thus suppressing the NF-κB signaling pathway and tumorigenesis. In addition, actin beta-like 2 (ACTBL2) competes with RBCK1 for MTSS1 binding, leading to p65 stabilization. Importantly, MTSS1 silencing promotes patient-derived organoid formation and xenograft growth. MTSS1 downregulation in clinical tumors is also linked to worse prognosis. Overall our data reveal a new paradigm of NF-κB regulation and may have important implications in therapeutics targeting TICs.Entities:
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Year: 2020 PMID： 35122005 DOI： 10.1038/s43018-019-0021-y
Source DB: PubMed Journal: Nat Cancer ISSN： 2662-1347