GREM2 maintains stem cell-like phenotypes in gastric cancer cells by regulating the JNK signaling pathway
Authors: Ao Ran
Lin Guan
Jiani Wang
Ying Wang
Journal: Cell Cycle (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: GREM2; JNK signaling pathway; biological properties; gastric cancer stem cells.
Affiliations: The First Affiliated Hospital of China Medical University, Shenyang, P.R. China

Abstract:  Gastric cancer (GC) is one of the major malignancies worldwide. This study was conducted to explore the mechanism by which GREM2 maintains biological properties of GC stem cells (GCSCs), and proved that GREM2 could potentially regulate the proliferation, apoptosis, invasion, migration and tumorigenic ability of GCSCs through the regulation of the JNK signaling pathway. In silico analysis was utilized to retrieve expression microarray related to GC, and differential analysis was conducted. The cell line with the highest GREM2 expression was overexpressed with GREM2 mimic, silencing GREM2 by siRNA, or treated with activator or inhibitor of the JNK signaling pathway. Subsequently, expression of GREM2, JNK signaling pathway-, apoptosis- or migration and invasion-associated factors were determined. Proliferation, migration, invasion, apoptosis of GCSCs in vitro and tumorigenic ability and lymph node metastasis of GCSCs in vivo were determined. Based on the in silico analysis of GSE49051, GREM2 was determined to be overexpressed in GC and its expression was the highest in the MKN-45 cell line, which was selected for the subsequent experiments. Silencing of GREM2 or inhibition of the JNK signaling pathway suppressed the proliferation, migration and invasion, while promoting apoptosis of GCSCs in vitro as well as inhibiting tumorigenesis and lymph node metastasis in vivo. In conclusion, the aforementioned findings suggest that the silencing of GREM2 suppresses the activation of the JNK signaling pathway, thereby inhibiting tumor progression. Therefore, GREM2-mediated JNK signaling pathway was expected to be a new therapeutic strategy for GC. 

Retracted: Yes

PubPeer comments:
 Figure 2 contains duplicated data. Identical data for D2 - - mice (white triangles) appear both in A and in B, even though these are purportedly two different experiments, at two different levels of magnesium. It s the same data, with same sequence of values and same sequence of error bars, which does not seem possible if they were truly obtained in different experiments. Here is panel B:  And here is panel B with the D2 - - data copied from panel A, in red (after stretching slightly to match the different y scale):  , 
 And here is panel B with the D2 - - data copied from panel A, in red (after stretching slightly to match the different y scale):  , 
 This issue refers to a review article written almost 20 years ago regarding older findings. For these reasons, we do not have anymore access to the original data. Actually, it seems likely that we used the same data from D2- - mice for the two graphs, which were built using data obtained from several sets of experiments done at different times by different people, hence the possible confusion for which we apologize. As a further explanation of this mistake, in this review article we did not aim of course at presenting original data, but only wanted to give a very general view of the role of dopamine in striatal plasticity (block of LTD by this manipulation, enhancement of LTP by this other manipulation, etc.), based on data generated by our group and by others in other publications, and confirmed by several other groups in the following years. We agree that, by choosing to present these data as they were original data, we did not choose the best way to convey this information. , 
 #3 * by choosing to present these data as they were original data, we did not choose the best way to convey this information. * I suspect that Austromusotima Camptozonale is not so much worried about the repetition of the D2 - - data points in Figs 2A and 2B, and more worried that they are labeled as coming from different conditions.  It may be that the problem is simply that the legend is misleading. ,