Open AccessSGCE Promotes Breast Cancer Stem Cells by Stabilizing EGFR
Author(s) -
Zhao Lina,
Qiu Ting,
Jiang Dewei,
Xu Haibo,
Zou Li,
Yang Qin,
Chen Ceshi,
Jiao Baowei
Publication year - 2020
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201903700
Subject(s) - cd44 , cancer research , cancer stem cell , stem cell , biology , metastasis , ubiquitin ligase , cancer , microbiology and biotechnology , cell , ubiquitin , biochemistry , genetics , gene
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.