RETRACTED: Identification of FOXN4 as a tumor suppressor of breast carcinogenesis via the activation of TP53 and deactivation of Notch signalling
Authors: Dan Su
Zhiquan Qin
Xiao Wang
Zheling Chen
Journal: Gene (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Breast tumorigenesis; FOXN4; Notch inhibitor; TP53/FOXN4 tumor suppressors; Therapeutics.
Affiliations: Department of Medical Oncology, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou 310014, Zhejiang Province, PR China., Department of Medical Oncology, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou 310014, Zhejiang Province, PR China. Electronic address: .

Abstract:  Objective: Fork head domain-containing transcription factor family (FOX), is comprised of &gt;20 members. Members of FOX family have been implicated in a wide range of physiological and/or diseased conditions. Many of FOX members have been shown to be involved in tumorigenesis and progression. The potential roles in carcinogenesis of FOXN4, a member as one of the vast FOX family, remains relatively unknown. Method: Here, we explored the potential involvement of FOXN4 in breast cancer. Results: First, observed that a higher FOXN4 was identified in the normal adjacent breast tissue as compared to that in the breast cancer samples; an increased FOXN4 level was associated with a better prognosis in patients with breast cancer. In addition, ectopically expression of FOXN4 led to the decreased cell proliferation, reduced colony formation and metastatic abilities (EMT, migration and invasion) in breast cancer cell lines. Furthermore, we showed the direct interaction between FOXN4 and TP53 and FOXN4 binding led to the increased activity of TP53. Silencing FOXN4 led to reduced TP53 and increased expression of Dll4, Notch and survivin, providing a link between FOXN4 and Notch signaling. Finally, we used patient-derived xenograft mouse model to demonstrate the tumor inhibitory effects of Notch-inhibitor, PF-3084014. We found that PF-3084014 treatment led to a significantly smaller tumor burden and higher survival ratio in patient-derived xenograft mice as compared to the vehicle. This tumor suppressive effect was accompanied by the increased expression of TP53, FOXN4 and decreased Dll4 and Notch. Conclusion: Collectively, our data strongly suggested the tumor suppressive roles of FOXN4 in breast tumorigenesis via the activation of TP53 while suppressing Notch signaling. Future studies are warranted to explore the clinical application of PF-3084104 (Notch inhibitor) for the treatment of breast cancer patients. 

Retracted: Yes

PubPeer comments:
 Retracted [15 February 2021] . -------------------------------------------- This article has been retracted: please see Elsevier Policy on Article Withdrawal (http: www.elsevier.com locate withdrawalpolicy). This article has been retracted at the request of the Editors-in-Chief. The article has a high level of similarity to another article published in Oncotargets and Therapy, u2018FOXN4 Inhibits Breast Cancer Progression By Direct Activation Of P53u2019 (Onco Targets Ther. 2020; 13: 71u201381; doi:10.2147 OTT.S206775). In particular, the data presented in Table 1 of both publications appears to be the same data and the reference lists are nearly identical. The article published in Oncotargets and Therapy was submitted and accepted first, but the Editors-in-Chief note that the submission to Gene was made before the Oncotargets and Therapy article was published. Gene has tried to contact the authors of this article but at the time of publication of this notice the journal has not received any response. As there is no explanation for the similarity between these two publications the Editors-in-Chief of Gene have lost confidence in the validity of this work and have decided to retract it. ,