GABRP sustains the stemness of triple-negative breast cancer cells through EGFR signaling
Li, XY; Wang, HR; Yang, X; Wang, XQ; Zhao, LA; Zou, L; Yang, Q; Hou, ZL; Tan, J; Zhang, HL; Nie, JY; Jiao, BW
2021
发表期刊CANCER LETTERS
ISSN0304-3835
卷号514页码:90-102
摘要Effective treatment regimens for triple-negative breast cancer (TNBC) are relatively scarce due to a lack of specific therapeutic targets. Epidermal growth factor receptor (EGFR) signaling is highly active in TNBC and is associated with poor prognosis. Most EGFR antagonists, which significantly improve outcome in lung and colon cancer, have shown limited clinical effects in breast cancer. However, limiting EGFR expression in TNBC is a potential strategy for improving the clinical efficacy of EGFR antagonists. Here, we found that the gammaaminobutyric acid type A receptor pi subunit (GABRP), as a membrane protein enriched in TNBC stem cells, interacted with EGFR and significantly sustained its expression, resulting in stemness maintenance and chemotherapy resistance. Silencing GABRP induced down-regulation of EGFR signaling, which hindered cell stemness and enhanced sensitivity to chemotherapies, including paclitaxel, doxorubicin, and cisplatin. We also identified that retigabine, an FDA-approved drug for adjunctive treatment of seizures, increased the sensitivity of EGFR to gefitinib in gefitinib-resistant cells. Our findings show that GABRP can sustain the stemness of TNBC via modulating EGFR expression, suggesting that GABRP may be a potential therapeutic target that can address EGFR inhibitor resistance in TNBC.
收录类别sci
语种英语
文献类型期刊论文
条目标识符http://ir.kiz.ac.cn/handle/152453/13636
专题科研部门_发育的印迹调控与进化学(焦保卫)
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GB/T 7714
Li, XY,Wang, HR,Yang, X,et al. GABRP sustains the stemness of triple-negative breast cancer cells through EGFR signaling[J]. CANCER LETTERS,2021,514:90-102.
APA Li, XY.,Wang, HR.,Yang, X.,Wang, XQ.,Zhao, LA.,...&Jiao, BW.(2021).GABRP sustains the stemness of triple-negative breast cancer cells through EGFR signaling.CANCER LETTERS,514,90-102.
MLA Li, XY,et al."GABRP sustains the stemness of triple-negative breast cancer cells through EGFR signaling".CANCER LETTERS 514(2021):90-102.
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