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
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.
基金:
National Natural Science Foundation of China [81602585]; Science and Technology Planning Project of Guangdong Province [2021A1515010124, 2017A030313522]; Fundamental Research Funds for the Central Universities [18ykpy13]; Guangzhou Science and Technology Plan Project (Basic and Applied Basic Research) [202102080617]; Kelin Nova Program of The First Affiliated Hospital of Sun Yat-sen University; Shenzhen Fundamental Research Program [JCYJ2019081280001770]
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
通讯作者:
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
推荐引用方式(GB/T 7714):
Wang Ling-Ling,Wan Xiao-Yun,Wang Tao-Li,et al.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[J].MEDICAL ONCOLOGY.2022,39(12):doi:10.1007/s12032-022-01859-w.
APA:
Wang, Ling-Ling,Wan, Xiao-Yun,Wang, Tao-Li,Liu, Chun-Qi&Zheng, Fei-Meng.(2022).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.MEDICAL ONCOLOGY,39,(12)
MLA:
Wang, Ling-Ling,et al."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".MEDICAL ONCOLOGY 39..12(2022)