CK2α/CSNK2A1 Induces Resistance to Doxorubicin through SIRT6-Mediated Activation of the DNA Damage Repair Pathway
CK2α/CSNK2A1 is involved in cancer progression by phosphorylating various signaling molecules. Considering the role of CSNK2A1 in cancer progression and the phosphorylation of SIRT6 and the role of SIRT6 in chemoresistance through the DNA damage repair pathway, CSNK2A1 and SIRT6 might be involved in...
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MDPI AG
2021-07-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/7/1770 |
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| author | Usama Khamis Hussein Asmaa Gamal Ahmed Yiping Song Kyoung Min Kim Young Jae Moon Ae-Ri Ahn Ho Sung Park Su Jin Ahn See-Hyoung Park Jung Ryul Kim Kyu Yun Jang |
| author_facet | Usama Khamis Hussein Asmaa Gamal Ahmed Yiping Song Kyoung Min Kim Young Jae Moon Ae-Ri Ahn Ho Sung Park Su Jin Ahn See-Hyoung Park Jung Ryul Kim Kyu Yun Jang |
| author_sort | Usama Khamis Hussein |
| collection | DOAJ |
| description | CK2α/CSNK2A1 is involved in cancer progression by phosphorylating various signaling molecules. Considering the role of CSNK2A1 in cancer progression and the phosphorylation of SIRT6 and the role of SIRT6 in chemoresistance through the DNA damage repair pathway, CSNK2A1 and SIRT6 might be involved in resistance to conventional anti-cancer therapies. We evaluated the expression of CSNK2A1 and phosphorylated SIRT6 in the 37 osteosarcoma patients and investigated the effects of CSNK2A1 and the phosphorylation of SIRT6 on Ser338 on resistance to the anti-cancer effects of doxorubicin. Higher expression of CSNK2A1 and phosphorylated SIRT6 was associated with shorter survival in osteosarcoma patients. U2OS and KHOS/NP osteosarcoma cells with induced overexpression of CSNK2A1 were resistant to the cytotoxic effects of doxorubicin, and the knock-down of CSNK2A1 potentiated the cytotoxic effects of doxorubicin. CSNK2A1 overexpression-mediated resistance to doxorubicin was associated with SIRT6 phosphorylation and the induction of the DNA damage repair pathway molecules. CSNK2A1- and SIRT6-mediated resistance to doxorubicin in vivo was attenuated via mutation of SIRT6 at the Ser338 phosphorylation site. Emodin, a CSNK2A1 inhibitor, potentiated the cytotoxic effects of doxorubicin in osteosarcoma cells. This study suggests that blocking the CSNK2A1-SIRT6-DNA damage repair pathway might be a new therapeutic stratagem for osteosarcomas. |
| first_indexed | 2024-03-10T09:43:30Z |
| format | Article |
| id | doaj.art-d00de330cfda439b97d16c244b80174f |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T09:43:30Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-d00de330cfda439b97d16c244b80174f2023-11-22T03:29:48ZengMDPI AGCells2073-44092021-07-01107177010.3390/cells10071770CK2α/CSNK2A1 Induces Resistance to Doxorubicin through SIRT6-Mediated Activation of the DNA Damage Repair PathwayUsama Khamis Hussein0Asmaa Gamal Ahmed1Yiping Song2Kyoung Min Kim3Young Jae Moon4Ae-Ri Ahn5Ho Sung Park6Su Jin Ahn7See-Hyoung Park8Jung Ryul Kim9Kyu Yun Jang10Department of Pathology, Jeonbuk National University Medical School, Jeonju 54896, KoreaDepartment of Pathology, Jeonbuk National University Medical School, Jeonju 54896, KoreaDepartment of Orthopedic Surgery, Jeonbuk National University Medical School, Jeonju 54896, KoreaDepartment of Pathology, Jeonbuk National University Medical School, Jeonju 54896, KoreaResearch Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, KoreaDepartment of Pathology, Jeonbuk National University Medical School, Jeonju 54896, KoreaDepartment of Pathology, Jeonbuk National University Medical School, Jeonju 54896, KoreaDepartment of Biochemistry and Molecular Biology, Jeonbuk National University Medical School, Jeonju 54896, KoreaDepartment of Bio and Chemical Engineering, Hongik University, Sejong 30016, KoreaResearch Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, KoreaDepartment of Pathology, Jeonbuk National University Medical School, Jeonju 54896, KoreaCK2α/CSNK2A1 is involved in cancer progression by phosphorylating various signaling molecules. Considering the role of CSNK2A1 in cancer progression and the phosphorylation of SIRT6 and the role of SIRT6 in chemoresistance through the DNA damage repair pathway, CSNK2A1 and SIRT6 might be involved in resistance to conventional anti-cancer therapies. We evaluated the expression of CSNK2A1 and phosphorylated SIRT6 in the 37 osteosarcoma patients and investigated the effects of CSNK2A1 and the phosphorylation of SIRT6 on Ser338 on resistance to the anti-cancer effects of doxorubicin. Higher expression of CSNK2A1 and phosphorylated SIRT6 was associated with shorter survival in osteosarcoma patients. U2OS and KHOS/NP osteosarcoma cells with induced overexpression of CSNK2A1 were resistant to the cytotoxic effects of doxorubicin, and the knock-down of CSNK2A1 potentiated the cytotoxic effects of doxorubicin. CSNK2A1 overexpression-mediated resistance to doxorubicin was associated with SIRT6 phosphorylation and the induction of the DNA damage repair pathway molecules. CSNK2A1- and SIRT6-mediated resistance to doxorubicin in vivo was attenuated via mutation of SIRT6 at the Ser338 phosphorylation site. Emodin, a CSNK2A1 inhibitor, potentiated the cytotoxic effects of doxorubicin in osteosarcoma cells. This study suggests that blocking the CSNK2A1-SIRT6-DNA damage repair pathway might be a new therapeutic stratagem for osteosarcomas.https://www.mdpi.com/2073-4409/10/7/1770osteosarcomaCSNK2A1SIRT6doxorubicinDNA damageprognosis |
| spellingShingle | Usama Khamis Hussein Asmaa Gamal Ahmed Yiping Song Kyoung Min Kim Young Jae Moon Ae-Ri Ahn Ho Sung Park Su Jin Ahn See-Hyoung Park Jung Ryul Kim Kyu Yun Jang CK2α/CSNK2A1 Induces Resistance to Doxorubicin through SIRT6-Mediated Activation of the DNA Damage Repair Pathway Cells osteosarcoma CSNK2A1 SIRT6 doxorubicin DNA damage prognosis |
| title | CK2α/CSNK2A1 Induces Resistance to Doxorubicin through SIRT6-Mediated Activation of the DNA Damage Repair Pathway |
| title_full | CK2α/CSNK2A1 Induces Resistance to Doxorubicin through SIRT6-Mediated Activation of the DNA Damage Repair Pathway |
| title_fullStr | CK2α/CSNK2A1 Induces Resistance to Doxorubicin through SIRT6-Mediated Activation of the DNA Damage Repair Pathway |
| title_full_unstemmed | CK2α/CSNK2A1 Induces Resistance to Doxorubicin through SIRT6-Mediated Activation of the DNA Damage Repair Pathway |
| title_short | CK2α/CSNK2A1 Induces Resistance to Doxorubicin through SIRT6-Mediated Activation of the DNA Damage Repair Pathway |
| title_sort | ck2α csnk2a1 induces resistance to doxorubicin through sirt6 mediated activation of the dna damage repair pathway |
| topic | osteosarcoma CSNK2A1 SIRT6 doxorubicin DNA damage prognosis |
| url | https://www.mdpi.com/2073-4409/10/7/1770 |
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