Association of human breast cancer CD44-/CD24- cells with delayed distant metastasis
| Autor: | Qingtian Ma, Caigang Liu, Ce Ji, Jie Yang, Yixiao Zhang, Guanglei Chen, Haixin Lei, Hao Zhang, Liping Ai, Xi Gu, Yongliang Yang, Lisha Sun, Jinqi Xue, Xinbo Qiao |
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| Rok vydání: | 2021 |
| Předmět: |
cancer stem cell
QH301-705.5 Science General Biochemistry Genetics and Molecular Biology Metastasis Breast cancer Cancer stem cell medicine Biology (General) skin and connective tissue diseases delayed recurrence General Immunology and Microbiology biology CD24 business.industry General Neuroscience CD44 Cancer General Medicine medicine.disease Cancer cell Cancer research biology.protein Medicine convertion Stem cell business RHBDL2 |
| Zdroj: | eLife, Vol 10 (2021) |
| ISSN: | 2050-084X |
| DOI: | 10.7554/elife.65418 |
| Popis: | Tumor metastasis remains the main cause of breast cancer-related deaths, especially delayed breast cancer distant metastasis. The current study assessed the frequency of CD44-/CD24-breast cancer cells in 576 tissue specimens for associations with clinicopathological features and metastasis and investigated the underlying molecular mechanisms. The results indicated that higher frequency (≥19.5%) of CD44-/CD24-cells was associated with delayed postoperative breast cancer metastasis. Furthermore, CD44-/CD24-triple negative breast cancer (TNBC) cells spontaneously converted into CD44+/CD24-cancer stem cells (CSCs) with properties similar to CD44+/CD24-CSCs from primary human breast cancer cells and parental TNBC cells in terms of stemness marker expression, self-renewal, differentiation, tumorigenicity, and lung metastasis in vitro andin NOD/SCID mice. RNA sequencing identified several differentially expressed genes (DEGs) in newly converted CSCs andRHBDL2, one of the DEGs, expression was upregulated. More importantly,RHBDL2silencing inhibited the YAP1/USP31/NF-κB signaling and attenuated spontaneous CD44-/CD24-cell conversion into CSCs and their mammosphere formation. These findings suggest that the frequency of CD44-/CD24-tumor cells andRHBDL2may be valuable for prognosis of delayed breast cancer metastasis, particularly for TNBC. |
| Databáze: | OpenAIRE |
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