Lentivirus-mediated shRNA targeting Nanog inhibits cell proliferation and attenuates cancer stem cell activities in breast cancer.
Emerging evidences suggest that cancer stem cells (CSCs) are responsible for tumor growth, metastasis and treatment resistance. Nanog is one of the transcription factors that are essential for stem cellular physiology process. Previous studies reported that Nanog was detected in breast cancer and other solid tumors and indicated that it has oncogenic characteristics. However, expression feature of Nanog in breast cancer stem cells (BCSCs) enriched population and its biological function in BCSCs is poorly understood. In this study, CD44 + CD24- fraction sorting with Fluorescence Activated Cell Sorter and mammosphere culture were used for enriching BCSCs. We report here that Nanog was highly expressed in CSCs-enriched population from the breast cancer cells, as well as stemness-associated genes. In addition, we employed the lentivirus-mediated shRNA targeting Nanog to investigate function of Nanog in BCSCs. We found that targeted inhibition of Nanog could suppress proliferation and colony formation in breast cancer cells. Further studies showed that targeted inhibition of Nanog resulted in a decrease of BCSCs activities, including mammosphere formation, CD44 + CD24- proportion and expressions of stemness-associated genes. These data therefore suggest that Nanog possesses important function in BCSCs and targeted inhibition of Nanog may provide a novel means of targeting and eliminating BCSCs.
a Department of Oncology , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , P.R. China .
Chun
C
Hu
a Department of Oncology , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , P.R. China .|b Department of Oncology , Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine , Suzhou , P.R. China .
Liang
L
Xu
a Department of Oncology , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , P.R. China .|b Department of Oncology , Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine , Suzhou , P.R. China .
Shujing
S
Liang
b Department of Oncology , Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine , Suzhou , P.R. China .|c Graduate School of Xuzhou Medical College , Xuzhou , P.R. China , and.
Zhiying
Z
Zhang
d Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine , Shanghai , P.R. China.
Yanyun
Y
Zhang
a Department of Oncology , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , P.R. China .|b Department of Oncology , Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine , Suzhou , P.R. China .
Fengchun
F
Zhang
D001943:Breast Neoplasms / Q000378:metabolism* / Q000628:therapy*; D051927:CD24 Antigen / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D057809:HEK293 Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D016086:Lentivirus / Q000378:metabolism*; D061986:MCF-7 Cells; D000071317:Nanog Homeobox Protein / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage*
D051927:CD24 Antigen; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D034741:RNA, Small Interfering
Breast cancer; Nanog; RNA interference; cancer stem cells; targeted therapy