癌症干细胞
癌症
CD44细胞
癌细胞
生物
医学
三阴性乳腺癌
细胞生长
细胞生物学
雌激素受体
作者
Lina Zhao,Ting Qiu,Dewei Jiang,Haibo Xu,Li Zou,Qin Yang,Ceshi Chen,Baowei Jiao
标识
DOI:10.1002/advs.201903700
摘要
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 CD24lowCD44high and high aldehyde dehydrogenase 1 (ALDH1) cell subpopulation (CD24lowCD44high ALDH1+) exhibit very high tumor initiating capacity. In the current study, the upregulated genes are analyzed in both CD24lowCD44high 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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