CD44细胞
癌症研究
癌变
癌症干细胞
乳腺癌
生物
基因沉默
转移
染色质免疫沉淀
CD24型
干细胞
癌症
医学
内科学
发起人
细胞生物学
细胞
基因表达
基因
生物化学
遗传学
作者
Kanakaraju Marumudi,Ragini Yeeravalli,Komal Kaushik,Digvijay Singh,Bhupendra Mehra,Nitin Gangane,Anupama Gupta,Kalyan Goswami,Amitava Das
标识
DOI:10.1016/j.bbadis.2021.166228
摘要
Breast cancer stem cells (CSCs) are distinct CD44+-subpopulations that are involved in metastasis and chemoresistance. However, the underlying molecular mechanism of CD44 in breast CSCs-mediated tumorigenesis remains elusive. We observed high CD44 expression in advanced-stage clinical breast tumor samples. CD44 activation in breast CSCs sorted from various triple negative breast cancer (TNBC) cell lines induced proliferation, migration, invasion, mammosphere formation that were reversed in presence of inhibitor, 4-methyl umbelliferone or CD44 silencing. CD44 activation in breast CSCs induced Src, Akt, and nuclear translocation of pSTAT3. PCR arrays revealed differential expression of a metabolic gene, Lipoprotein lipase (LPL), and transcription factor, SNAI3. Differential transcriptional regulation of LPL by pSTAT3 and SNAI3 was confirmed by promoter-reporter and chromatin immunoprecipitation analysis. Orthotopic xenograft murine breast tumor model revealed high tumorigenicity of CD24−/CD44+-breast CSCs as compared with CD24+-breast cancer cells. Furthermore, stable breast CSCs-CD44 shRNA and/or intratumoral administration of Tetrahydrolipstatin (LPL inhibitor) abrogated tumor progression and neoangiogenesis. Thus, LPL serves as a potential target for an efficacious therapeutics against aggressive breast cancer.
科研通智能强力驱动
Strongly Powered by AbleSci AI