Association of human breast cancer CD44-/CD24- cells with delayed distant metastasis

Author:

Qiao Xinbo1ORCID,Zhang Yixiao12,Sun Lisha1ORCID,Ma Qingtian1,Yang Jie1,Ai Liping1,Xue Jinqi1,Chen Guanglei1,Zhang Hao13,Ji Ce14,Gu Xi1,Lei Haixin5,Yang Yongliang6,Liu Caigang1ORCID

Affiliation:

1. Department of Oncology, Shengjing Hospital, China Medical University, Shenyang, China

2. Dapartment of Urology, Shengjing Hospital, China Medical University, Shenyang, China

3. Department of Breast Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China

4. Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang, China

5. Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China

6. Center for Molecular Medicine, School of Life Science and Biotechnology, Dalian University of Technology, Dalian, China

Abstract

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.

Funder

National Science Foundation

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference52 articles.

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