Silence of HDAC6 suppressed esophageal squamous cell carcinoma proliferation and migration by disrupting chaperone function of HSP90
Authors: Hua-Lin Chen
Zong-Wen Sun
Yuan-Yuan Chen
Ming Chen
Hua Tao
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: HDAC6; HSP90; esophageal carcinoma; motility; proliferation.
Affiliations: Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P.R. China., Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu, P.R. China., Department of Radiotherapy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, P.R. China.

Abstract:  Esophageal carcinoma is aggressive in nature and its prognosis is largely dependent on the degree of invasion. Histone deacetylase 6 (HDAC6), as the most unique member of HDACs family, has the positive activity to promote initiation and progression of various cancers via targeting multiple non-histone proteins in cytoplasm. In this study, we found that HDAC6 was over-expressed in three esophageal cancer cell lines (KYSE140, KYSE170, KYSE180) when compared to non-carcinoma esophageal epithelial cell HEEC-1. Then two HDAC6 specific siRNAs and HDAC6 inhibitor tubastatin A greatly suppressed KYSE140 and KYSE180 cells proliferation and migration, and the inhibition of cell motility was accompanied by elevated acetylation of α-tubulin, a target of HDAC6. Consistently, the microtubulin skeleton was stabilized after HDAC6 knockdown or inhibition. In addition, acetylation status of HSP90, another HDAC6 target, was also increased towards HDAC6 knockdown or inhibition by co-immunoprecipitation assay. Besides, co-treatment of HSP90 inhibitor (PU-H71) and HDAC6 inhibitor (tubastatin A) induced a stronger cell migration inhibition compared to administration of either drug alone. Furthermore, cell proliferation of KYSE140 and KYSE180 were also compromised in response to combination of HDAC6 and HSP90 inhibitors. Additionally, co-administration of HSP90 inhibitor and HDAC6 inhibitor strongly inhibited tumor growth in vivo. Taken together, our results indicated that HDAC6 is a promising target by inhibiting HSP90 function in ESCC. 

Retracted: Yes

PubPeer comments:
 Possibly an error in selection of images for Fig 6B. ![file] , 
 Thank you for the comments on our experimental results. We have examined the raw data immediately, and found that this is indeed our mistake. The specific problems and reasons are as follows: In the process of the experiment, each group of experiments repeated three times, and the same slide will be photographed many times in different fields of vision, inevitably there will be regional overlap. I mistakenly placed the repeated experiment of Tubastatin + PU-H71 of KYSE140 cell lines in Tubastatin + PU-H71 of KYSE180 cell lines. We will contact the journal editor to apologize for the error and replace the data. Best wishes! Dr Ming Chen , 
 #2 I am glad that the minor error is easily fixed! Please forgive my pedantic need for perfection. , 
 Thank you very much for your comments and help us find the error, so that we can correct the data in time. I wish you all the best in your work. , 
 Retracted, December 2021: https: onlinelibrary.wiley.com doi 10.1002 jcb.30183  The above article, published online on 17 April 2018 in Wiley Online Library , has been retracted by agreement between the authors, the journal s Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed after the authors asked to correct the article. An investigation revealed several flaws and inconsistencies between results presented and experimental methods described, thus the editors consider the conclusions of this article to be invalid. ,