Autor: |
Xinbo Qiao, Yixiao Zhang, Lisha Sun, Qingtian Ma, Jie Yang, Liping Ai, Jinqi Xue, Guanglei Chen, Hao Zhang, Ce Ji, Xi Gu, Haixin Lei, Yongliang Yang, Caigang Liu |
Jazyk: |
angličtina |
Rok vydání: |
2021 |
Předmět: |
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Zdroj: |
eLife, Vol 10 (2021) |
Druh dokumentu: |
article |
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 and in NOD/SCID mice. RNA sequencing identified several differentially expressed genes (DEGs) in newly converted CSCs and RHBDL2, one of the DEGs, expression was upregulated. More importantly, RHBDL2 silencing 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 and RHBDL2 may be valuable for prognosis of delayed breast cancer metastasis, particularly for TNBC. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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