Inhibitor 9 Combined With Androgen Deprivation Therapy or Chemotherapy Delays the Malignant Behavior of Castration-Resistant Prostate Cancer Through K-Ras/PLCε/PKCε Signaling Pathway
Authors: Chunli Luo
Bo Qiao
Zhen Quan
Yingying Gao
Ting Li
Jiayu Liu
Limei Duan
Yongbo Zheng
Jinxiao Yang
Luo Li
Xiaohou Wu
Journal: Frontiers in Oncology (2020)
Discipline: CLINICAL MEDICINE
Keywords: KRAS mutation G12C; castration-resistant prostate cancer; drug resistance; inhibitor 9; metastasis.
Affiliations: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China., Department of Laboratory Diagnosis, Chongqing Medical University, Chongqing, China., Department of Laboratory Diagnosis, Clinical Medical College, Jiamusi University, Heilongjiang, China., Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China., Department of Laboratory Diagnosis, Chongqing Public Health Medical Treatment Center, Chongqing, China.

Abstract:  Castration-resistant prostate cancer (CRPC) is a progressed stage of prostate cancer, which requires better understanding of the mechanisms and remains an unmet clinical need. As a common oncogene, K-Ras is associated with malignant behavior in different types of tumors but its role in CRPC is unknown. The present study aims to find the mechanism of K-Ras in CRPC and whether it can be used as a crucial molecule for the treatment of CRPC. For this purpose, tissue samples from primary prostate cancer (PPC) and CRPC patients were analyzed by immunohistochemistry and the data showed that K-Ras was elevated in CRPC. More importantly, higher K-Ras expression was related to a shorter recurrence-free survival time in patients with CRPC. In addition, K-Ras promoted the invasion, migration, and drug resistance of CRPC cells by activation of PLCε/PKCε signaling pathway. Meanwhile, the inhibitor of K-RasG12C mutants was able to inhibit malignant behavior of CRPC cells in vitro and in vivo. Inhibitors of K-RasG12C mutants have entered clinical trials. Taken together, the study shows that K-Ras may activate PKCε through PLCε, resulting in the alterations of malignant behavior of CRPC. Inhibitor 9, an inhibitor of the K-RasG12C mutant, has a strong anti-tumor effect in CRPC, which potentially suggests that inhibitors of this nature may serve as a promising treatment for CRPC. 

Retracted: Yes

PubPeer comments:
 Figure 5c appears to have an image overlap. *** ![file] , 
 Dear Actinopolyspora Biskrensis, Thank you for your reminder and kindly comments. It s our mistakes for inappropriate images. We will prepare for checking our manuscript and original datas. And soon we wil correct our mistakes and connect the periodical office for putting the right images. Sincerely yours, Xiaohou Wu , 
 #2 Thank you very much for your reply. Could the authors please share the contact information for the organization responsible for misconduct investigations at your institution or your funding agency? I have not been able to find that online. Would it be someone at MOST? Many thanks. *** ![file] , 
 Dear Actinopolyspora Biskrensis, Thanks very much for your concern about our study. We are terribly sorry for making such mistakes.After receiving your comments, We immediately carried out self-examination of the whole study and checked our primary data and found out that indeed there was an inappropriate image in the publication which we have conducted an investigation in our groups. These mistakes happened when we collected the raw data and some pictures needed further processing.During the process, we mistook this image. However, after repeated verification of the test and the original data, we found that our data and results are still true and reliable.In addition, this part was verified by two groups of different cell lines, and consistent results were obtained.we sincerely apologize for the careless oversight which had not been identified before publication. Again, thank you for your concern and we have already contacted the journal to prepare an erratum about it. Here is the right images and graph. ![file] , 
 #4 Thank you for your reply. Unfortunately, this paper has more issues than the one I identified above. Another example shows below. Two images of mice are of the same animal with one image appearing stretched horizontally and cropped differently. In addition, the luminescence is different suggesting that this was not nearly an error during figure assembly. These types of errors are sometimes seen in papermill papers. *** ![file] *** Enhanced brightness to show identical backgrounds ![file] , 
 Dear Actinopolyspora Biskrensis, Thanks very much for your concern about our study. As you know you can see this graph have an obvious figure assembly with the numeber 42 put the wrong position. Besides,most of the funding for our experiments comes from individuals and the living imaging is very expensive and in our lab , we only can download our images from our administrator not allowed for using this machine. So to ensure the success rate of the experimentuff0cevery time we captured every mice for thrice at set intervals.Because of the large experimental data, the administrator made a mistake for grouping when download these figures. We have already found this wrong figure and cantacted to the journal before you told us. Meanwhile, all the raw data are saved in our team,once you pointed the mistakes we can reply immediatily. so our paper definitely can not be from papermill papers.Meanwhile,we keep the records of the experiments. We resolutely boycott the papermill papers as you do. And our data and results are still true and reliable. Again, thank you for your concern and improve quality of our experiment. Here is the right images and graph. ![file] ![file] , 
 #6 Thank you for your reply and for providing the new images. u201dWe resolutely boycott the papermill papers as you do.u201d Could anyone reading this help us uncover some papermill details? For example, can you point to a website where they advertise? Do you have evidence that a particular lab of unethically selling their services for authors to publish papers? Can you point us to papers that are products of a papermill? If you prefer to remain anonymous this information can be sent to: CheshireGrins@protonmail.com , 
 Retracted, [31 May 2021] . ------------------------ This retracts the article  Inhibitor 9 Combined With Androgen Deprivation Therapy or Chemotherapy Delays the Malignant Behavior of Castration-Resistant Prostate Cancer Through K-Ras PLCu03b5 PKCu03b5 Signaling Pathway in volume 10, 75. Please find the retraction statement below: Following publication, concerns were raised regarding image manipulation and duplication. The authors failed to provide a satisfactory explanation during the investigation, which was conducted in accordance with Frontiersu2019 policies. This retraction was approved by the Chief Editors of Frontiers in Oncology and Chief Executive Editor. The authors agreed to this retraction. ,