Suppression of YAP by DDP disrupts colon tumor progression
Authors: Dan Jin
Chengxia Liu
Jiwei Guo
Chengyong Qin
Yan Wu
Kun Li
Hong Jiang
Journal: Oncology Reports (2018)
Discipline: CLINICAL MEDICINE
Keywords: Colon cancer; YAP; drug resistance; prognosis; cisplatin
Affiliations: Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China., Cancer Research Institute, Binzhou Medical University Hospital, Binzhou, Shandong 256603, P.R. China., Department of Pain Management, Binzhou Medical University Hospital, Binzhou, Shandong 256603, P.R. China., Department of Anorectal Surgery, Binzhou Medical University Hospital, Binzhou, Shandong 256603, P.R. China., Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, Shandong 256603, P.R. China.

Abstract:  Colon cancer is a commonly diagnosed cancer that often has a poor prognosis. Combined with the development of drug resistance to cancer treatment agents the treatment efficacy of colon cancer can be limited. Activation of the oncogene YAP has been shown to be related to colon cancer progression and is associated with poor prognosis, drug resistance and metastasis, even under treatment. Cisplatin (DDP) is a commonly used drug that can control carcinoma progression, although its mechanisms are poorly understood. In the present study, we examined whether DDP specifically suppressed YAP in order to inhibit colon carcinoma progression. Our data revealed that Mst/Yap signaling was unusually activated in colon cancers, promoting cell proliferation and invasion. DDP treatment decreased the expression of YAP at both the transcriptional and post-translational levels, leading to cell cycle arrest, apoptosis and senescence in cancer cells, in addition to decreasing epithelial-to-mesenchymal transition, cell motility and in vitro cell invasion and migration. Ultimately, DDP increased the expression of E-cadherin and decreased the expression of vimentin. The present study also revealed that post-translational regulation of YAP phosphorylation controlled the subcellular distribution between the nucleus and the cytoplasm. In conclusion, the findings of the present study revealed that DDP was a suitable therapeutic candidate for colon cancer that specifically targets the Mst/Yap signaling pathway. 

Retracted: Yes

PubPeer comments:
 Two images in figure 6D appear to overlap, although they are described differently. *** ![file] *** ![file] , 
 Dear Actinopolyspora Biskrensis, thank you so much for helping us to point out the error. We have checked our original data of clone formation images and found that this error was caused by our carelessness with wrongly copy the image of DDP groups to the siYAP groups when prepared figures. We apologize for such an error that shouldnu2019t being made however I would like to mention that this error does not affect the conclusions of the study. The authors have requested the Journal to give an erratum. and thank you again for the comments. The original data for Figure 6D are shown below. ![file] , 
 The colony forming assays in Figure 4d seem to overlap with images from another of the authors papers: https: pubpeer.com publications 30C4B226FBDA768041AF53AB1F391A ![file] , 
 There are additional duplications in the histopathology images. ![file] (I had to do some cropping to reduce the image size.) , 
 Retracted Oncol Rep 39: [Related article:] 2114-2126, 2018; DOI: 10.3892 or.2018.6297 Following the publication of this paper, it was drawn to the authorsu2019 attention by an interested reader that Fig. 6D contained images featuring overlapping data, which reportedly had been derived under different experimental conditions. Subsequently, further issues of data duplication were brought to light by another interested reader concerning the above article; first, certain of the images showing colony-forming assays in Fig. 4D were strikingly similar to images that had appeared in a previous publication by the same research group, and secondly, a couple of instances of data duplication were identified among the histopathological images presented within Fig. 7D. After having considered the various issues that have been brought to light with this paper, together with an appeal from the authors that a Corrigendum be published, the Editor of Oncology Reports has ruled that the article should be retracted from the publication on account of a lack of overall confidence in the presented data. Note that the authors were not in agreement that the number of errors reported and identified were sufficient to merit the retraction of the article. Additionally, the authors carefully checked the raw data and drew a conclusion that the final scientific conclusions were not affected. The Editor and the authors apologize to the readership for any inconvenience caused. ,