PPA1 promotes NSCLC progression via a JNK- and TP53-dependent manner
Authors: Yanpei Chen
Wenzhi Shen
Shuang Yang
Wei Liu
Xiaojun Wang
Chaoyang Zhang
Yonghua Bao
Huimin Jiang
Xiaoyuan Zhang
Wen Shi
Wancai Yang
Tianyin Qu
Daishun Liu
Dehong Luo
Dong Ou
Liying Yuan
Hui Wang
Journal: Oncogenesis (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Inorganic pyrophosphatase; tumor progression; lung carcinoma; NSCLC; cell apoptosis
Affiliations: The Third Affiliated Hospital of Zunyi Medical University/ First People's Hospital of Zunyi, Zunyi, 563200, China., Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Medical College of Nankai University, Tianjin, 300071, China., Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining, 272067, China., Zunyi Medical College, Zunyi, 563006, China., Department of Radiation Oncology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000, China., Department of Biochemical Engineering, School of Chemical Engineering & Technology, Tianjin University, Tianjin, 300072, China., Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining, 272067, China. ., Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Medical College of Nankai University, Tianjin, 300071, China. .

Abstract:  Inorganic pyrophosphatase (PPA1) promotes tumor progression in several tumor types. However, the underlying mechanism remains elusive. Here, we disclosed that PPA1 expression is markedly upregulated in lung carcinoma tissue versus normal lung tissue. We also found that the non-small cell lung cancer (NSCLC) cell lines show increased PPA1 expression levels versus normal lung cell line control. Moreover, the knockdown of PPA1 promotes cell apoptosis and inhibits cell proliferation. Whereas, the ectopic expression of PPA1 reduces cell apoptosis and enhances cell proliferation. Most interestingly, the expression of mutant PPA1 (D117A) significantly abolishes PPA1-mediated effect on cell apoptosis and proliferation. The underlying mechanism demonstrated that TP53 expression deficiency or JNK inhibitor treatment could abolish PPA1-mediated NSCLC progression. In summary, the aforementioned findings in this study suggest a new pathway the PPA1 mediates NSCLC progression either via TP53 or JNK. Most important, the pyrophosphatase activity is indispensible for PPA1-mediated NSCLC progression. This may provide a promising target for NSCLC therapy. 

Retracted: No

PubPeer comments:
 The wrong western blot data was used in Fig. 2d and Fig. 3d in this Article. The correct versions of the figures are provided below. The scientific conclusions of this paper were not affected. ![file] , 
 There may also be another issue. Figure 2E and Figure 3E appear to have a similar sample, but I believe they are described differently. In any case, could the authors review the images in those figures just to be sure? *** 2E ![file] *** 3E ![file] , 
 Figures 2I and 6F may have some unexpected similarities. Could the authors please review? *** Closeup ![file] *** ![file] ![file] , 
 #1 Thank you for your comments. The first author of this paper (Ms. Dehong Luo) published her first PPA1 paper in Cancer Medicine in 2016 (please see in https: pubmed.ncbi.nlm.nih.gov 27666431 ), in the Cancer Medicine paper, the author detected PPA1 expression in various tumor types and she also found PPA1 expression change could effect TP53 and caspase 3 expression simply. In this Oncogensis paper, she investigated the function and mechanism of PPA1 in regulating NSCLC cell apoptosis, but she used the same TP53 caspase 3 expression data with above. After we published, we found this question, so we made this correction. As we described: the wrong western blot data was used in Fig. 2d and Fig. 3d in this article, the scientific conclusions of this paper were not affected. #2 Thank you for your pointing this out. We checked the original data as soon as possible, we found that we put the DAPI single staining images in the wrong order unintentionally, because the three images in each group could not overlayed. We are very sorry that we may provide the wrong final version to the publisher. The correct version was as below, we have contacted the journal and applied for correction. ![file] #3 Thank you for your pointing this out. We checked the analysis record as soon as possible, we found that the two images were from different samples as below, as each group has three repeats, we have used the other one to instead this image. ![file] ,