Cantharidin represses invasion of pancreatic cancer cells through accelerated degradation of MMP2 mRNA
Authors: Dao-Ming Li
Long-Pei Chen
Min Tao
Qiaoming Zhi
Meng Shen
Kai Chen
Wei Li
Yadi Wu
Fei-Ran Gong
Meng-Yao Wu
Journal: Scientific Reports (2015)
Discipline: Multidisciplinary
Keywords: Cantharidin; protein phosphatase 2A (PP2A); pancreatic cancer cells; matrix metalloproteinase 2 (MMP2); ERK
Affiliations: Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China., Department of General Surgery, the First Affiliated Hospital of Soochow University, Suzhou 215006, China., Department of Hematology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China., 1] Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China [2] Jiangsu Institute of Clinical Immunology, Suzhou 215006, China [3] Institute of Medical Biotechnology, Soochow University, Suzhou 215021, China [4] PREMED Key Laboratory for Precision Medicine, Soochow University, Suzhou 215021, China., 1] Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China [2] PREMED Key Laboratory for Precision Medicine, Soochow University, Suzhou 215021, China.

Abstract:  Cantharidin is an active constituent of mylabris, a traditional Chinese medicine, and is a potent and selective inhibitor of protein phosphatase 2A (PP2A) that plays an important role in cell cycle control, apoptosis, and cell-fate determination. In the present study, we found that cantharidin repressed the invasive ability of pancreatic cancer cells and downregulated matrix metalloproteinase 2 (MMP2) expression through multiple pathways, including ERK, JNK, PKC, NF-κB, and β-catenin. Interestingly, transcriptional activity of the MMP2 promoter increased after treatment with PP2A inhibitors, suggesting the involvement of a posttranscriptional mechanism. By using an mRNA stability assay, we found accelerated degradation of MMP2 mRNA after treatment of cantharidin. Microarray analyses revealed that multiple genes involved in the 3' → 5' decay pathway were upregulated, especially genes participating in cytoplasmic deadenylation. The elevation of these genes were further demonstrated to be executed through ERK, JNK, PKC, NF-κB, and β-catenin pathways. Knockdown of PARN, RHAU, and CNOT7, three critical members involved in cytoplasmic deadenylation, attenuated the downregulation of MMP2. Hence, we present the mechanism of repressed invasion by cantharidin and other PP2A inhibitors through increased degradation of MMP2 mRNA by elevated cytoplasmic deadenylation. 

Retracted: No

PubPeer comments:
 Figure 1A, 1B and 1K appears to have images which overlap. Roughly indicated with like-colored boxes. I am not certain that I located all of the possible overlaps. *** ![file] *** Full figure ![file] , 
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 The images in figure 1 A, B and K, representing different treatments, appear to be cut from a single source. (Only one image does not fit, but considering the missing parts it is likely that it belongs to the original source) ![file] , 
 February 25, 2021 u201cThis Article contains errors (sic) in Figure 1. As a result of mistakes in figure assembly, the IHC images shown in the published Figure 1 are incorrect and do not correspond to the experiments described. The correct Figure 1 appears below as Figure 1.u201d ![file] ,