PRRX1‐induced epithelial‐to‐mesenchymal transition in salivary adenoid cystic carcinoma activates the metabolic reprogramming of free fatty acids to promote invasion and metastasis
Authors: Yu Chen
Ya-Ling Tang
Sha-Sha Wang
Xin Pang
Mei Zhang
Jia-Shun Wu
Jing-Biao Wu
Ya-Jie Tang
Ya-Ping Jiang
Xin-Hua Liang
Journal: Cell Proliferation (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PRRX1; free fatty acids (FFAs); metabolism; metastasis; salivary adenoid cystic carcinoma (SACC).
Affiliations: State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, China., Department of Implant, The Affiliated Hospital of Qingdao University, Qingdao, China., State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China., Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, China.

Abstract:  Objectives: Increasing evidences demonstrate a close correlation between epithelial-to-mesenchymal transition (EMT) induction and cancer lipid metabolism. However, the molecular mechanisms have not been clarified. Materials and methods: In our study, the relative expression level of PRRX1 was detected, its relationship with free fatty acid (FFA) and PPARG2 was analysed in 85 SACC tissues and 15 salivary glands from the benign salivary tumours. We also compared the FFAs composition and levels in these SACC cells. PPARG2 was detected in PRRX1-induced FFAs treatment as well as Src and MMP-9 were detected in FFAs treatment-induced invasion and migration of SACC cells, and ChIP test was performed to identify the target interactions. Results: Our data showed that overexpression of PRRX1 induced EMT and facilitated the invasion and migration of SACC cells, and PRRX1 expression was closely associated with high FFAs level and poor prognosis of SACC patients. Furthermore, PRRX1 silence led to the increase of PPARG2 and the reduction of FFAs level and the migration and invasion of SACC cells. And inhibition of PPARG2 rescued FFAs level and migration and invasion capabilities of SACC cells. Free fatty acids treatment induced an increase of Stat5-DNA binding activity via Src- and MMP-9-dependent pathway. Conclusions: Collectively, our findings showed that the PRRX1/PPARG2/FFAs signalling in SACC was important for accelerating tumour metastasis through the induction of EMT and the metabolic reprogramming of FFAs. 

Retracted: No

PubPeer comments:
 Figure 5B appears to show some splicing and unexpected similarities. *** Enhanced brightness ![file] *** Equalized contrast to illustrate similarities ![file] *** Original ![file] , 
 Similar issue in 5C. *** ![file] , 
 Thanks for your information! We had carefully checked the figures and found that the figures were different. , 
 #3 Actinopolyspora Biskrensis in #1 and #2 talked about TWO things, unexpected similarity and splicing. A simple assertion that  the figures were different can t even address one of the two concerns. I believe that we scientists ought to make our argument with evidence, either for or against, as Actinopolyspora Biskrensis clearly demonstrated. Please provide your original uncropped films to substantiate your points. Thank you! , 
 #3 Thank you for your reply. As this is clearly not true, I will suggest the journal investigate. This lab appears to have more than a [dozen papers] with similar concerns. , 
 Corrigendum. First published: 30 September 2021  In Jiang et al.,1 the following errors were published on page 10. In the original version of this published article, the authors mistakenly used the bands of DNA ladder from the vector group of Src-Stat5 combination capacity detection as a ruler, to match the band position of DNA fragments extracted by ChIP in other three groups, which were the same batch experiments. After repeating the experiments, the authors obtained the correct data and the correct versions of Figure 5B and 5C are shown below. This correction does not change the result and conclusion. The authors apologize for these errors. ![file] *** I kid you not. This is what appears in the PDF and html version of the correction. I respectfully suggest that these results *would* change the conclusions and perhaps the journal can correct the correction. , 
 Just for the ease of readership, here is version of the figure in #6 with +40% brightness and -40% contrast. To my eye, there are still some striking similarities between some of the lanes, but admittedly I think this is basically the  noise floor of the image, so who knows. Also, if those bar charts are derived from the figures, I would love to know how, I mean 4 of the bars are almost exactly 10%, but I don t see a factor of ~4-5 difference between the intensities in the blots. ![file] ,