ECT2 Increases the stability of EGFR and Tumorigenicity by Inhibiting Grb2 Ubiquitination in Pancreatic Cancer
Authors: Shengtao Zhu
Shuilong Guo
Shuo Yang
Junxiong Wang
Shutian Zhang
Li Min
Journal: Frontiers in Oncology (2021)
Discipline: CLINICAL MEDICINE
Keywords: ECT2; EGFR; EMT; Grb2; PDAC
Affiliations: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China., Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China., National Clinical Research Centre for Digestive Diseases, Beijing, China., Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China.

Abstract:  The poor prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is associated with the invasion and metastasis of tumor cells. Epithelial cell transforming 2 (ECT2) is a guanine nucleotide exchange factor (GEF) of the Rho family of GTPases. It has also been reported that upregulation of ECT2 in pancreatic cancer, but the role and mechanism of ECT2 have not been previously determined. We found that ECT2 was significantly elevated in PDAC tissues and cells, correlated with more advanced AJCC stage, distant metastases, and overall survival of patients with PDAC. Inhibition and overexpression tests showed that ECT2 promoted proliferation, migration and invasion in vitro, and promoted tumor growth and metastasis in vivo. We determined that ECT2 was involved in the post-translational regulation of Grb2. ECT2 inhibited the degradation of Grb2 through deubiquitination. Furthermore, knockdown of ECT2 downregulated EGFR levels by accelerating EGFR degradation. EGF stimulation facilitated the formation of ECT2-Grb2 complex. Overall, our findings indicated that ECT2 could be used as a promising new therapeutic candidate for PDAC. 

Retracted: Yes

PubPeer comments:
 Figure 3 has several flaws: 1) In A, mock and NC are the same sample ![file] 2) In B, each of the two ECT2 images seemed to be put together from two images, as there is a break visible when zooming in (indicated by red arrows) ![file] 3) In C, mock and NC are the same sample ![file] , 
 Dear Heterochasta Lasioplaca, Thanks very much for your information. We ve just finished the investigation on the original data of this article. For the first and third concerns, the flaws were caused by inappropriate data management. The lax naming on the files of related images made the first author confuse the Mock and the NC groups when preparing the data to publish. For the second concern, the break of the image resulted from a stutter of the imaging system. During the investigation, we found other issues such as incomplete records of the experimental process and wrong clarification of the author s contribution. Even though I do not doubt the main scientific conclusions of this paper, I ve already contacted the editorial office to retract this paper due to the rigor of the scientific process. Yours sincerely, Shutian Zhang , 
 Dear Shutian Zhang, Thank you for your response. I think a retraction makes sense in this case. Also thanks for taking the initiative on starting the retraction process. , 
 -- Retracted -- https: www.frontiersin.org articles 10.3389 fonc.2021.734761 full ,