FMNL1 mediates nasopharyngeal carcinoma cell aggressiveness by epigenetically upregulating MTA1
Authors: Chen-Yuan Wang
Feng-Wei Wang
Chao-Nan Qian
Hai-Qiang Mai
Wen-Hui Chen
Jia-Xing Zhang
Lin-Quan Tang
Xiao-Han Jin
Dan Xie
Mu-Sheng Zeng
Hsiang-Fu Kung
Ling Guo
Yi-Guo Jiang
Yi-Ji Liao
Mu-Yan Cai
Cai-Ping Ren
Journal: Oncogene (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Formin-like protein 1 (FMNL1); hematopoietic malignancies; nasopharyngeal carcinoma (NPC); invadopodia formation; epithelial-mesenchymal transition (EMT)
Affiliations: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China., Department of Oncology, the First Affiliated Hospital, Jinan University, Guangzhou, China., Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China., Department of Oncology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China., Department of Nasopharyngeal Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China., The State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China., Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine; Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Changsha, China., State Key Laboratory of Oncology in South China, the Chinese University of Hong Kong, Hong Kong, China., State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. ., Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China. .

Abstract:  It has been suggested that formin-like protein 1 (FMNL1) plays an important role in the pathogenic process of several hematopoietic malignancies. In this study, we performed a series of in vivo and in vitro assays to elucidate the biological functions of FMNL1 and underlying mechanisms in human nasopharyngeal carcinoma (NPC) pathogenesis. Herein, we report that high expression of FMNL1 in NPC is positively associated with an aggressive disease and/or poor patient survival. Ectopic overexpression of FMNL1 in NPC cells substantially promoted cell invadopodia formation, epithelial-mesenchymal transition (EMT) and invasiveness, whereas depletion of FMNL1 potently suppressed NPC cells invadopodia formation, EMT, and invasive/metastatic capacities. We further show that FMNL1 could enhance NPC cell aggressiveness by increasing a key downstream target, the metastasis-associated protein 1 (MTA1) gene. Importantly, ectopic overexpression of FMNL1 in NPC cells markedly improved the binding of HDAC1 with Profilin2 in the cytoplasm and suppressed the enrichment of HDAC1 on the promoter of MTA1 and thereby, leading to an increased MTA1 transcription and expression. Furthermore, in addition to the amplification of FMNL1 gene, decreased level of miR-16 in NPCs is another critical mechanism to upregulate FMNL1 expression. These results, collectively, provide first-line of evidences that high expression of FMNL1, resulted from decreased miR-16 and/or MTA1 amplification, has a potent oncogenic role to drive the development and aggressive process of NPC by upregulating MTA1, and FMNL1 might be employed as a new prognostic biomarker and therapeutic target for human NPC. 

Retracted: No

PubPeer comments:
 Figures 2g and 3g appear to have an image which overlaps. *** ![file] *** ![file] , 
 Dear Sir Madam, I m the first author, named Wen-Hui Chen, of the article titled u201cFMNL1 mediates nasopharyngeal carcinoma cell aggressiveness by epigenetically upregulating MTA1u201d . we appreciate your valuable comments on our published paper (Oncogene (2018)). As we got the message from the email, we immediately checked the original data of the experiment in vivo. We are very sorry for that we made some careless mistakes for the overlap of Fig2g and Fig3g. This mistake occurred during the process of clipping a huge number of raw pictures. The images in Figure 2g were obtained from metastatic tumors in the lung of nude mice that originated S18-shFMNL1 cells injected via the tail vein. The images in Figure 3g should be from lung metastatic tumors of mice that originated S26-FMNL1- shMTA1 cells. After we carefully check the original data, we found that we mistook the picture from the lung metastatic tumors originated S18-shFMNL1 cells, and we have found the correct picture of lung metastatic tumors of mice originated S26-FMNL1- shMTA1 cells in our original data. We will contact the editorial office of the Journal, Oncogene, for this mistake and make the necessary corrections by issuing a corrigendum as soon as possible. The misuse of the picture from the lung metastatic tumors originated S18-shFMNL1 cells will not directly affect our hypothesis and results. We apologize again for our mistakes, and are grateful for your constructive comment and sincere gratitude for pointing out this mistake. In the future, we will do our best, with a more rigorous attitude, to review all current work and manuscript to prevent it from happening again. Sincerely yours, Wen-Hui Chen, Ph.D. E-mail: chenwh@sysucc.org.cn , 
 #2 I appreciate the authoru2019s reply. I believe I stopped my review of this groupu2019s papers before finishing the full list. I believe there are 10 or more papers with similar issues posted now. If most of these concerns are valid, it may make readers cautious about the conclusions that have been published. , 
 Correction Published: 25 March 2021 Following the publication of the above article, the authors (sic) noted an error in Fig. 3g (down, right), in which it should be from lung metastatic tumors of mice that originated S26-FMNL1-shMTA1 cells. However, we found that this image was duplicated and misused from S18-shFMNL1 cells in Fig. 2g (down, right). We apologize for any inconvenience caused by this careless error. This correction notice contains the original image from the lung metastatic tumors originated S26-FMNL1- shMTA1 cells, and was completely corrected in Fig. 3g. ![file] , 
 Dear Dr Biskrensis, Thank you very much for raising the concerns in a number of our papers. As the corresponding author of the papers, including this paper, I have responsibility for these errors, although they were unintentionally made after checking the raw data. I do apologize to the readers for any inconvenience and confusion that caused by these mistakes. We would like to express our most sincere gratitude for your kindly pointing out the oversights in our papers, and we are now doing our best to check our original data and try to correct all related errors in the articles. Thank you again! Sincerely yours, Corresponding author, Dan Xie ,