Abstract |
The histone methyltransferase SETDB1 catalyzes the addition of methyl groups to histone H3 at lysine 9, and upregulation of SETDB1 is associated with poor prognosis in cancer patients. Here, we describe how overexpression of SETDB1 contributes to colorectal cancer (CRC) tumorigenesis and drug resistance. We show that SETDB1 is upregulated in CRC, and its level correlates with poor clinical outcome. SETDB1 attenuation inhibits CRC cell proliferation Mechanistically, SETDB1 promotes cell proliferation by upregulating Akt activation. Further, SETDB1 is essential for the tumorigenic activity of Akt. Functional characterization revealed that inhibition of SETDB1 reduces cell growth in CRC resistant to targeted treatments in vitro and in vivo, KRAS-mutated CRC included. Taken together, our results indicate that SETDB1 is a major driver of CRC and may serve as a potential target for the treatment of KRAS-mutated CRC.
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Authors | Zhenlin Hou, Li Sun, Feng Xu, Fuqing Hu, Jingqin Lan, Da Song, Yongdong Feng, Jing Wang, Xuelai Luo, Junbo Hu, Guihua Wang |
Journal | Cancer letters
(Cancer Lett)
Vol. 487
Pg. 63-73
(09 01 2020)
ISSN: 1872-7980 [Electronic] Ireland |
PMID | 32473242
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2020 Elsevier B.V. All rights reserved. |
Chemical References |
- Histones
- Histone Methyltransferases
- Histone-Lysine N-Methyltransferase
- SETDB1 protein, human
- Cetuximab
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Topics |
- Aged
- Carcinogenesis
(drug effects)
- Cell Proliferation
(drug effects)
- Cetuximab
(administration & dosage)
- Colorectal Neoplasms
(drug therapy, genetics, pathology)
- Drug Resistance, Neoplasm
(drug effects)
- Female
- Gene Expression Regulation, Neoplastic
(drug effects)
- Histone Methyltransferases
(genetics)
- Histone-Lysine N-Methyltransferase
(genetics)
- Histones
(genetics)
- Humans
- Male
- Middle Aged
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