期刊
ADVANCED SCIENCE
卷 7, 期 14, 页码 -出版社
WILEY
DOI: 10.1002/advs.201903700
关键词
breast cancer stem cells; epidermal growth factor receptors; SGCE
资金
- National Key Research and Development Program of China [2016YFA0100900, 2018YFC2000400]
- National Natural Science Foundation of China [31970612, U1802285, 81872414, 81830087, U1602221, 31771516]
- Yunnan Applied Basic Research Key Projects [2015HA026, 2018FA002]
- CAS Light of West China Program [xbzg-zdsys-201909, xbzg-zdsys-201913]
- Project of Innovative Research Team of Yunnan Province [2019HC005]
Breast cancer stem cells (BCSCs) are responsible for resistance to chemotherapy, high degree of metastasis, and poor prognosis, especially in triple-negative breast cancer (TNBC). The CD24(low)CD44(high) and high aldehyde dehydrogenase 1 (ALDH1) cell subpopulation (CD24(low)CD44(high) ALDH1(+)) exhibit very high tumor initiating capacity. In the current study, the upregulated genes are analyzed in both CD24(low)CD44(high) and ALDH1(+) cell populations at single-cell resolution, and a highly expressed membrane protein, SGCE, is identified in both BCSC populations. Further results show that SGCE depletion reduces BCSC self-renewal, chemoresistance, and metastasis both in vitro and in vivo, partially through affecting the accumulation of extracellular matrix (ECM). For the underlying mechanism, SGCE functions as a sponge molecule for the interaction between epidermal growth factor receptor (EGFR) and its E3 ubiquitination ligase (c-Cbl), and thus inhibits EGFR lysosomal degradation to stabilize the EGFR protein. SGCE knockdown promotes sensitivity to EGFR tyrosine kinase inhibitors (TKIs), providing new clues for deciphering the current failure of targeting EGFR in clinical trials and highlighting a novel candidate for BCSC stemness regulation.
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