Co-targeting CK2α and YBX1 suppresses tumor progression by coordinated inhibition of the PI3K/AKT signaling pathway
Authors: Wen-Bin Ou
Hai-Meng Zhou
Yi-Cong Ma
Tianyi Qin
Wen-Fei Xu
Xue-Qi Fu
Ting-Ting Li
Long Shi
Jie Peng
Hang Mu
Hou-Shi Ma
Xu-Hui Li
Journal: Cell Cycle (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CK2α; YBX1; cancer.
Affiliations: College of Life Sciences, Jilin University, Changchun, China, Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Zhejiang, China, Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, China, Department of Geriatric Gastroenterology, Chinese People’s Liberation Army General Hospital, Beijing, China, Department of Biology, Georgetown Preparatory School, North Bethesda, USA

Abstract:  Protein kinase CK2 alpha (CK2α) is involved in the development of multiple malignancies. Overexpression of Y-box binding protein 1 (YBX1) is related to tumor proliferation, drug resistance, and poor prognosis. Studies have demonstrated that both CK2 and YBX1 could regulate the PI3K/AKT pathway. In addition, we predicted that CK2 might be the upstream kinase of YBX1 through the Human Protein Reference Database (HPRD). Herein, we hypothesize that CK2 may interact with YBX1 and they regulate the PI3K/AKT signaling pathway together. Expressions of CK2α and YBX1 in cancer cell lines were evaluated by immunoblotting. The results showed that CK2α could regulate the expression of YBX1 at the transcriptional level, which is dependent on its enzymatic activity. Synergistic effects of PI3K/AKT pathway inactivation could be observed through combined inhibition of CK2α and YBX1, and YBX1 was required for CK2α-induced PI3K/AKT pathway activation. Further results demonstrated that CK2α could interact with YBX1 and PI3K/AKT antagonist decreased cell resistance to doxorubicin induced by co-activation of CK2α and YBX1. These results indicated that combined inhibition of CK2α and YBX1 showed synergistic effects in inactivating the PI3K/AKT signaling pathway and may be one of the mechanisms involved in tumor growth and migration. 

Retracted: No

PubPeer comments:
 Fig 3f. ![file] A panel seems to have been duplicated. , 
 Dear Hoya Camphorifolia, This is Wenfei Xu, the first author of this paper. Thank you for pointing out the errors in Fig. 3f of our paper. We have thoroughly examined the experimental data of cell cycle assays (Fig. 3f) and found that the error was accidentally made in the process when we plotted the Fig. 3f with the obtained figures of Flow analysis because of our carelessness. For cell cycle analysis, we usually process the raw data with the Flow analysis software by data fitting of each group for figure presentation. In fig.3f, we wrongly reuse the image of CK2 inhibition (2.5 u03bcM CX4945+scramble shRNA) as the control group (DMSO+scramble shRNA). However, there is no problem with the obtained data of the control group (DMSO+scramble shRNA) and CK2 inhibition group (2.5 u03bcM CX4945+scramble shRNA) analyzed by the software, and the unintentional misuse does not affect the conclusion of the experiment. From a rigorous point of view, we replotted Fig. 3f with the original figures. This error has now been corrected as shown below. This correction will not change the description, interpretation, or original conclusions of the article. In addition, we have contacted the journal editorial office three times within a month to correct this mistake, and we haven t got a reply yet (maybe the editor doesnu2019t have enough time to reply to messages or make corrections in such a short time). We sincerely apologize for this mistake and any inconvenience caused. ![file] Sincerely Wenfei Xu ,