CUL4B promotes gastric cancer invasion and metastasis-involvement of upregulation of HER2
Authors: B Han
M Qi
H Liu
Y Zou
J Hu
J Mi
R Zhang
X Li
L Wang
M Jiao
L Liu
Y Gong
M Zhao
L Zhang
Journal: Oncogene (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cullin 4B; gastric cancer; HER2; tumor suppressor; metastasis
Affiliations: Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Pathology, Shandong University QiLu Medical College, School of Basic Medical Sciences, Jinan, Shandong, China., Department of Pathology, Shandong University Qilu hospital, Jinan, China., Department of Pathology, Binzhou People's Hospital, Binzhou, China., Research Center for Medicinal Biotechnology, Key Laboratory for Rare and Uncommon Diseases of Shandong Province, Shandong Academy of Medicinal Sciences, Jinan, China., The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Molecular Medicine and Genetics, Shandong University QiLu Medical College, School of Basic Medical Sciences, Jinan, China., Department of Pathology, Affiliated Hospital of Binzhou Medical College, Binzhou, China., Department of Pathology, Xintai Traditional Chinese Medicine Hospital, Taian, China.

Abstract:  Cullin 4B (CUL4B) is a scaffold protein overexpressed in several solid malignancies. It is known to silence tumor suppressor through post-transcriptional manner. However, its clinical significance and underlying molecular mechanisms in gastric cancer (GC) remain largely unknown. In this study, we found that CUL4B was significantly overexpressed in GC tissues and its overexpression was correlated with lymph node metastasis and poor prognosis. Through gain- and loss-of-function experiments, we showed that CUL4B promotes GC cell invasion and epithelial-mesenchymal transition (EMT) in vitro, as well as tumor growth and metastasis in vivo. Mechanistically, we identified HER2 as a downstream target gene of CUL4B in GC. CUL4B unregulated HER2 expression via transcriptionally repressing miR-125a. Intriguingly, HER2 inhibitors significantly reversed CUL4B-induced EMT in vitro and partially blocked GC metastasis in tumor xenografts with CUL4B overexpression. Finally, we suggested the involvement of the PI3K/AKT pathway in CUL4B-induced HER2 upregulation in GC. In all, we proposed a model for a CUL4B-miR-125a-HER2 oncoprotein axis, which provided novel insight into how HER2 was activated and contributed to GC progression and metastasis. 

Retracted: No

PubPeer comments:
 Figure 5k appears to have duplicate images ![file] , 
 Dear Dendrodoa Grossulariauff0c Iu2019m writing to you in response to recent inquiry you posted with regard to our article entitledu201cCUL4B promotes gastric cancer invasion and metastasis-involvement of upregulation of HER2u201duff0cwith me being the corresponding author. I appreciate your interest in our work. Upon being notified of your inquiry, we carefully re-examine our manuscripts and raw data and lab records. We regret that transwell images of the Flag4B group and FlagB+NC group in Figure 5K are duplicate in our published article. This was due to mistake in preparing the results. We mistakenly copied the data of the Flag4B group as the FlagB+NC group. We have restored the correct transwell images in figure 5K as below. This correction does not influence the results of our studyu2019s conclusion. We sincerely apologize for any inconvenience caused. We will be communicating this issue to the Journal s Editor-in-Chief and will post an update when a decision is made. Yours sincerely Bo Original results of AGS cells are shown below: ![file] The correct figures of Figure5K are as follows: ![file] ,