G protein-coupled receptor 87 (GPR87) promotes the growth and metastasis of CD133⁺ cancer stem-like cells in hepatocellular carcinoma
Authors: Lixing Zhang
Ying Cui
Fangyu Zhao
Guoping Jiang
Jinjun Li
Haiyang Xie
Ming Yao
Miaoxin Zhu
Mingxia Yan
Hong Li
Taoyang Chen
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Hepatocellular carcinoma; Cancer stem cells; CD133; Metastasis; GPR87
Affiliations: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Abstract:  Hepatocellular carcinoma (HCC) is a prevalent disease worldwide, and the majority of HCC-related deaths occur due to local invasion and distant metastasis. Cancer stem cells (CSCs) are a small subpopulation of cancer cells that have been hypothesized to be responsible for metastatic disease. Recently, we and others have identified a CSC population from human HCC cell lines and xenograft tumors characterized by their expression of CD133. However, the precise molecular mechanisms by which CD133(+) cancer stem-like cells mediate HCC metastasis have not been sufficiently analyzed. Here, we have sorted HCC cells using CD133 as a cancer stem cell (CSC) marker by magnetic-activated cell sorting (MACS) and demonstrated that the CD133(+) HCC cells not only possess greater migratory and invasive capacity in vitro but are also endowed with enhanced metastatic capacity in vivo and in human HCC specimens when compared to CD133(-) HCC cells. Gene expression analysis of the CD133(+) and CD133(-) cells of the HCC line SMMC-7721 revealed that G protein-coupled receptor 87 (GPR87) is highly expressed in CD133(+) HCC cells. In this study, we explored the role of GPR87 in the regulation of CD133 expression. We demonstrated that the overexpression of GPR87 up-regulated CD133 expression, promoted CSC-associated migratory and invasive properties in vitro, and increased tumor initiation in vivo. Conversely, silencing of GPR87 expression reduced the levels of CD133 expression. Conclusion: GPR87 promotes the growth and metastasis of CD133(+) cancer stem-like cells, and our findings may reveal new targets for HCC prevention or therapy. 

Retracted: No

PubPeer comments:
 Figure 1D and 4D. * Red boxes: Four panels appear to look identical but represent different experiments. ![file] , 
 Figure S6. * Blue boxes: In the top row ( Migtatory ), two panels appear to look very similar ![file] , 
 Dear Dr. Elisabeth M Bik We are extremely grateful for your findings to our error in this paper. We have checked and found the cause of the error, as you pointed out u201cFour panels appear to look identical but represent different experimentsu201d (Fig 1D and Fig 4D are same, although the bar graphs are different and correct), This is caused by our carelessness when preparing Figure 1D by Photoshop, with the same original pictures copy paste (wrong folder selected). In Fig 6S, the cause of error is same. We are terribly sorry for the mistakes and have corrected Figure 1D and Fig 6S attached here and also apply for errata to the journal. On receive Erratum Website link, we will attach it here. Many thanks again for your comments and we will avoid similar mistakes from happening in the future. Best regards, Corrected Figures: Fig 1D ![file] Fig 6S ![file] ,