Co-targeting CK2α and YBX1 suppresses tumor progression by coordinated inhibition of the PI3K/AKT signaling pathway
| Autor: | Hou-Shi Ma, Xue-Qi Fu, Xu-Hui Li, Wen-Bin Ou, Long Shi, Tianyi Qin, Wen-Fei Xu, Yi-Cong Ma, Ting-Ting Li, Hai-Meng Zhou, Jie Peng, Hang Mu |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Alpha (ethology) Biology 03 medical and health sciences Phosphatidylinositol 3-Kinases 0302 clinical medicine Cell Movement Neoplasms medicine Humans Doxorubicin Casein Kinase II Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Kinase Akt/PKB signaling pathway Binding protein Cell Biology Hep G2 Cells Cell biology Gene Expression Regulation Neoplastic Oncogene Protein v-akt 030104 developmental biology Tumor progression Drug Resistance Neoplasm 030220 oncology & carcinogenesis Y-Box-Binding Protein 1 Developmental Biology medicine.drug HeLa Cells Protein Binding Signal Transduction Research Paper |
| Zdroj: | Cell Cycle |
| ISSN: | 1551-4005 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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