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NDR1 activates CD47 transcription by increasing protein stability and nuclear location of ASCL1 to enhance cancer stem cell properties and evasion of phagocytosis in small cell lung cancer

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机构: [1]Sun Yat Sen Univ, Affiliated Hosp 1, Dept Med Oncol, Eastern Hosp, 58 Zhong Shan Er Lu, Guangzhou 510080, Peoples R China [2]Sun Yat Sen Univ, Affiliated Hosp 1, Guangdong Prov Key Lab Orthoped & Traumatol, Guangzhou, Peoples R China [3]Guangzhou Univ Chinese Med, Guangzhou, Peoples R China [4]Guangzhou Univ Chinese Med, Dept Oncol, Clin Med Coll 4, Shenzhen 518033, Peoples R China [5]Panyu Cent Hosp, Dept Thorac Surg, Guangzhou, Peoples R China
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关键词: NDR1 Small cell lung cancer Cancer stem cell Phagocytosis CD47 ASCL1

摘要:
Small cell lung cancer (SCLC) is one of the most malignant types of lung cancer. Cancer stem cell (CSC) and tumor immune evasion are critical for the development of SCLC. We previously reported that NDR1 enhances breast CSC properties. NDR1 might also have a role in the regulation of immune responses. In the current study, we explore the function of NDR1 in the control of CSC properties and evasion of phagocytosis in SCLC. We find that NDR1 enhances the enrichment of the ALDEFLUOR(high) and CD133(high) population, and promotes sphere formation in SCLC cells. Additionally, NDR1 upregulates CD47 expression to enhance evasion of phagocytosis in SCLC. Furthermore, the effects of NDR1 enhanced CD47 expression and evasion of phagocytosis are more prominent in CSC than in non-CSC. Importantly, NDR1 promotes ASCL1 expression to enhance NDR1-promoted CSC properties and evasion of phagocytosis in SCLC cells. Mechanically, NDR1 enhances protein stability and the nuclear location of ASCL1 to activate the transcription of CD47 in SCLC. Finally, CD47-blocking antibody can be used to target NDR1 enhanced CSC properties and evasion of phagocytosis by suppressing EGFR activation in SCLC. In summary, our data indicate that NDR1 could be a critical factor for modulating CSC properties and phagocytosis in SCLC.

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出版当年[2021]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
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出版当年[2020]版:
Q3 ONCOLOGY
最新[2023]版:
Q2 ONCOLOGY

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第一作者机构: [1]Sun Yat Sen Univ, Affiliated Hosp 1, Dept Med Oncol, Eastern Hosp, 58 Zhong Shan Er Lu, Guangzhou 510080, Peoples R China [2]Sun Yat Sen Univ, Affiliated Hosp 1, Guangdong Prov Key Lab Orthoped & Traumatol, Guangzhou, Peoples R China
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通讯机构: [1]Sun Yat Sen Univ, Affiliated Hosp 1, Dept Med Oncol, Eastern Hosp, 58 Zhong Shan Er Lu, Guangzhou 510080, Peoples R China [2]Sun Yat Sen Univ, Affiliated Hosp 1, Guangdong Prov Key Lab Orthoped & Traumatol, Guangzhou, Peoples R China
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