Journal article
SETDB1 in cancer: overexpression and its therapeutic implications
American journal of cancer research, Vol.11(5), pp.1803-1827
01/01/2021
PMID: 34094655
Abstract
SET Domain Bifurcated Histone Lysine Methyltransferase 1 (SETDB1, ESET, KMT1E) is a H3K9 methyltransferase involved in gene silencing. In recent years, SETDB1 has been implicated as an oncogene in various cancers, highlighting a critical need to better understand the mechanisms underlying SETDB1 amplification, overexpression, and activation. In the following review, we first examine the history of SETDB1, starting from its discovery in 1999 and ending with recent findings. We follow with an outline of the structure and subcellular location of SETDB1, as well as potential mechanisms for regulation of its nuclear transport. Subsequently, we introduce SETDB1's various functions, including its roles in promyelocytic leukemia nuclear body (PML-NB) formation, the methylation and activation of Akt, the silencing of the androgen receptor (AR) gene, retroelement silencing, the inhibition of tumor suppressor p53, and its role in promoting intestinal differentiation and survival. The Cancer Cell Line Encyclopedia (CCLE) screened SETDB1 dependency in 796 cancer cell lines, identifying SETDB1 as a common essential gene in 531 of them, demonstrating that SETDB1 expression is critical for the survival of the majority of cancers. Therefore, we provide a detailed review of the oncogenic effects of SETDB1 overexpression in breast cancer, non-small cell lung cancer, prostate cancer, colorectal cancer, acute myeloid leukemia, glioma, melanoma, pancreatic ductal adenocarcinoma, liver cancer, nasopharyngeal carcinoma, gastric carcinoma, and endometrial cancer. Accordingly, we review several methods that have been used to target SETDB1, such as using Mithramycin A, Mithralog EC-8042, 3'-deazaneplanocin A (DZNep), and paclitaxel. Finally, we conclude by highlighting remaining gaps in knowledge and challenges surrounding SETDB1. Ultimately, our review captures the wide scope of findings on SETDB1's history, function, its implications in cancer, and provides suggestions for future research in the field.
Keywords: AKT; ATF7IP; SETDB1; histone methyltransferase.
Details
- Title: Subtitle
- SETDB1 in cancer: overexpression and its therapeutic implications
- Creators
- Vanessa J Lazaro-Camp - Univ Iowa, Carver Coll Med, Dept Pathol, MERF 5234,375 Newton Rd, Iowa City, IA 52242 USAKiarash Salari - Univ Iowa, Carver Coll Med, Dept Pathol, MERF 5234,375 Newton Rd, Iowa City, IA 52242 USAXiangbing Meng - Univ Iowa, Carver Coll Med, Dept Pathol, MERF 5234,375 Newton Rd, Iowa City, IA 52242 USAShujie Yang - Univ Iowa, Carver Coll Med, Dept Pathol, MERF 5234,375 Newton Rd, Iowa City, IA 52242 USA
- Resource Type
- Journal article
- Publication Details
- American journal of cancer research, Vol.11(5), pp.1803-1827
- PMID
- 34094655
- ISSN
- 2156-6976
- eISSN
- 2156-6976
- Language
- English
- Date published
- 01/01/2021
- Academic Unit
- Pathology
- Record Identifier
- 9984201249402771
Metrics
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