CHI-KAT8i5 suppresses ESCC tumor growth by inhibiting KAT8-mediated c-Myc stability
Summary: The integrated analysis of histone modifier enzymes in solid tumors, especially in esophageal squamous cell carcinoma (ESCC), is still inadequate. Here, we investigate the expression levels of histone modifier enzymes in ESCC tissues. Notably, KAT8 (lysine acetyltransferase 8) is identified...
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Elsevier
2025-01-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724014864 |
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| author | Dandan Zhang Ming Jiang Pan Li Kyle Vaughn Laster Dengyun Zhao Yafei Zhi Huifang Wei Wenna Nie Yunfeng Gao Qiong Wu Pu Xiang Xinyu He Kangdong Liu Zigang Dong |
| author_facet | Dandan Zhang Ming Jiang Pan Li Kyle Vaughn Laster Dengyun Zhao Yafei Zhi Huifang Wei Wenna Nie Yunfeng Gao Qiong Wu Pu Xiang Xinyu He Kangdong Liu Zigang Dong |
| author_sort | Dandan Zhang |
| collection | DOAJ |
| description | Summary: The integrated analysis of histone modifier enzymes in solid tumors, especially in esophageal squamous cell carcinoma (ESCC), is still inadequate. Here, we investigate the expression levels of histone modifier enzymes in ESCC tissues. Notably, KAT8 (lysine acetyltransferase 8) is identified as a prognostic and therapeutic biomarker in ESCC. Esophageal-tissue-specific deletion of KAT8 in mice led to less tumor burden after induction of tumorigenesis via 4-nitroquinoline N-oxide (4NQO) treatment compared with wild-type mice. Meanwhile, silencing KAT8 significantly suppresses tumor growth in cell-line-derived xenograft (CDX) and patient-derived xenograft (PDX) models. Mechanically, we confirm that KAT8 regulates c-Myc protein stability by directly binding it. Furthermore, we design and screen a specific KAT8 inhibitor (CHI-KAT8i5) that significantly attenuates tumor growth in vitro and in vivo, providing promising potential for clinical application. Thus, our work identifies that KAT8 could serve as a potential clinically relevant biomarker and therapeutic target in patients with ESCC and that KAT8 inhibitor is a promising lead candidate for ESCC therapy. |
| format | Article |
| id | doaj-art-dc2eb92189784c6383d3aa55bf369453 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-dc2eb92189784c6383d3aa55bf3694532025-01-09T06:13:48ZengElsevierCell Reports2211-12472025-01-01441115135CHI-KAT8i5 suppresses ESCC tumor growth by inhibiting KAT8-mediated c-Myc stabilityDandan Zhang0Ming Jiang1Pan Li2Kyle Vaughn Laster3Dengyun Zhao4Yafei Zhi5Huifang Wei6Wenna Nie7Yunfeng Gao8Qiong Wu9Pu Xiang10Xinyu He11Kangdong Liu12Zigang Dong13Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000 Henan, China; China-US (Henan) Hormel Cancer Institute, No. 127, Zhengzhou 450000 Henan, ChinaChina-US (Henan) Hormel Cancer Institute, No. 127, Zhengzhou 450000 Henan, ChinaChina-US (Henan) Hormel Cancer Institute, No. 127, Zhengzhou 450000 Henan, ChinaChina-US (Henan) Hormel Cancer Institute, No. 127, Zhengzhou 450000 Henan, ChinaDepartment of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000 Henan, China; China-US (Henan) Hormel Cancer Institute, No. 127, Zhengzhou 450000 Henan, ChinaDepartment of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000 Henan, China; China-US (Henan) Hormel Cancer Institute, No. 127, Zhengzhou 450000 Henan, ChinaDepartment of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000 Henan, China; China-US (Henan) Hormel Cancer Institute, No. 127, Zhengzhou 450000 Henan, ChinaChina-US (Henan) Hormel Cancer Institute, No. 127, Zhengzhou 450000 Henan, ChinaChina-US (Henan) Hormel Cancer Institute, No. 127, Zhengzhou 450000 Henan, ChinaDepartment of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000 Henan, China; China-US (Henan) Hormel Cancer Institute, No. 127, Zhengzhou 450000 Henan, ChinaDepartment of Hematology, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450000 Henan, ChinaDepartment of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000 Henan, China; China-US (Henan) Hormel Cancer Institute, No. 127, Zhengzhou 450000 Henan, ChinaDepartment of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000 Henan, China; China-US (Henan) Hormel Cancer Institute, No. 127, Zhengzhou 450000 Henan, China; The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou 450000 Henan, China; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou 450000 Henan, China; Corresponding authorDepartment of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000 Henan, China; China-US (Henan) Hormel Cancer Institute, No. 127, Zhengzhou 450000 Henan, China; The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou 450000 Henan, China; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou 450000 Henan, China; Corresponding authorSummary: The integrated analysis of histone modifier enzymes in solid tumors, especially in esophageal squamous cell carcinoma (ESCC), is still inadequate. Here, we investigate the expression levels of histone modifier enzymes in ESCC tissues. Notably, KAT8 (lysine acetyltransferase 8) is identified as a prognostic and therapeutic biomarker in ESCC. Esophageal-tissue-specific deletion of KAT8 in mice led to less tumor burden after induction of tumorigenesis via 4-nitroquinoline N-oxide (4NQO) treatment compared with wild-type mice. Meanwhile, silencing KAT8 significantly suppresses tumor growth in cell-line-derived xenograft (CDX) and patient-derived xenograft (PDX) models. Mechanically, we confirm that KAT8 regulates c-Myc protein stability by directly binding it. Furthermore, we design and screen a specific KAT8 inhibitor (CHI-KAT8i5) that significantly attenuates tumor growth in vitro and in vivo, providing promising potential for clinical application. Thus, our work identifies that KAT8 could serve as a potential clinically relevant biomarker and therapeutic target in patients with ESCC and that KAT8 inhibitor is a promising lead candidate for ESCC therapy.http://www.sciencedirect.com/science/article/pii/S2211124724014864CP: Cancer |
| spellingShingle | Dandan Zhang Ming Jiang Pan Li Kyle Vaughn Laster Dengyun Zhao Yafei Zhi Huifang Wei Wenna Nie Yunfeng Gao Qiong Wu Pu Xiang Xinyu He Kangdong Liu Zigang Dong CHI-KAT8i5 suppresses ESCC tumor growth by inhibiting KAT8-mediated c-Myc stability Cell Reports CP: Cancer |
| title | CHI-KAT8i5 suppresses ESCC tumor growth by inhibiting KAT8-mediated c-Myc stability |
| title_full | CHI-KAT8i5 suppresses ESCC tumor growth by inhibiting KAT8-mediated c-Myc stability |
| title_fullStr | CHI-KAT8i5 suppresses ESCC tumor growth by inhibiting KAT8-mediated c-Myc stability |
| title_full_unstemmed | CHI-KAT8i5 suppresses ESCC tumor growth by inhibiting KAT8-mediated c-Myc stability |
| title_short | CHI-KAT8i5 suppresses ESCC tumor growth by inhibiting KAT8-mediated c-Myc stability |
| title_sort | chi kat8i5 suppresses escc tumor growth by inhibiting kat8 mediated c myc stability |
| topic | CP: Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724014864 |
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