USP47 maintains the stemness of colorectal cancer cells and is inhibited by parthenolide
| Autor: | Ling-Mei Kong, Yan Li, Dongmei Fan, Shaohua Zhang, Xiaoman Ju, Yiying Zhu, Qihong Yang, Guifeng Su |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Homeobox protein NANOG Carcinogenesis Colorectal cancer Biophysics Apoptosis medicine.disease_cause Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cancer stem cell Cell Line Tumor Humans Medicine Gene silencing Parthenolide Gene Silencing Molecular Biology biology business.industry CD44 Cell Biology Prognosis medicine.disease Up-Regulation Gene Expression Regulation Neoplastic 030104 developmental biology chemistry 030220 oncology & carcinogenesis embryonic structures Neoplastic Stem Cells biology.protein Cancer research Ubiquitin-Specific Proteases Stem cell Colorectal Neoplasms business Sesquiterpenes Ubiquitin Thiolesterase Protein Binding |
| Zdroj: | Biochemical and Biophysical Research Communications. 562:21-28 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2021.05.017 |
| Popis: | Colorectal cancer stem cells (CCSCs) are implicated in colorectal tumor initiation, invasion, recurrence and treatment resistance, so elucidation of the mechanism underlying the cancer stem cells induction and development of drugs targeting CCSCs are vital for cancer treatment. Growing evidence shows that dysregulated deubiquitinase (DUBs) expression is frequently associated with stemness and maintenance of cancer stem cells (CSCs). In the current study, we found that upregulation of USP47 is associated with tumorigenesis and poor prognosis in clinical patients with colorectal cancer (CRC). Besides, USP47 was highly expressed in CCSCs enriched by serum-free culture. Further investigation showed that USP47 is closely involved in the maintenance of the stemness of CCSCs. USP47 silencing reduces proliferation and migration of colorectal cancer cells and suppresses the self-renewal of CCSCs by downregulating the expression of cancer stem cell markers, including CD44, CD133, CD166, OCT4 and NANOG. Furthermore, we identified Parthenolide (PTL), a natural sesquiterpene lactone, as a novel USP47 inhibitor. PTL diminishes CCSCs self-renewal and induces apoptosis of CCSCs. Taken together, our findings highlighted a novel DUB involved in the modulation of CCSCs stemness and the potential of PTL in the CRC treatment by targeting CCSCs as the USP47 inhibitor. |
| Databáze: | OpenAIRE |
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