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 over-expression 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.
第一作者单位：[1]Huazhong Univ Sci & Technol,Tongji Hosp,GI Canc Res Inst,Wuhan 430030,Peoples R China[3]Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Dept Colorectal Surg, State Key Lab Oncol South China,Canc Ctr, Guangzhou 510060, Peoples R China
通讯作者：
推荐引用方式(GB/T 7714)：
Hou Zhenlin,Sun Li,Xu Feng,et al.Blocking histone methyltransferase SETDB1 inhibits tumorigenesis and enhances cetuximab sensitivity in colorectal cancer[J].CANCER LETTERS.2020,487:63-73.doi:10.1016/j.canlet.2020.05.029.
APA：
Hou, Zhenlin,Sun, Li,Xu, Feng,Hu, Fuqing,Lan, Jingqin...&Wang, Guihua.(2020).Blocking histone methyltransferase SETDB1 inhibits tumorigenesis and enhances cetuximab sensitivity in colorectal cancer.CANCER LETTERS,487,
MLA：
Hou, Zhenlin,et al."Blocking histone methyltransferase SETDB1 inhibits tumorigenesis and enhances cetuximab sensitivity in colorectal cancer".CANCER LETTERS 487.(2020):63-73
医学