Abstract
Worldwide, cancer is the second leading cause of mortality after cardiovascular diseases. Among the numerous malignant tumors in human, digestive system cancers are the primary cause of morbidity and mortality. Acetylation and deacetylation are crucially involved in cancer occurrence and development; in addition, the deacetylation process is regulated by histone deacetylases (HDACs). Among the 18 human HDACs that have been reported, HDAC6 has been widely studied. There is upregulated HDAC6 expression in numerous types of tumor tissues and is closely associated with clinicopathological characteristics. Moreover, several HDAC6 inhibitors have been identified; furthermore, there has been extensive research on their ability to inhibit the growth of many tumors. This review summarizes the roles of HDAC6 in different primary digestive system malignancies.
Highlights
Gastrointestinal cancers involve various diseases, with many having poor prognoses
This review focuses on recent studies of HDAC6 in gastrointestinal cancers, including esophageal, gastric, colorectal, liver, and pancreatic cancer, as well as cholangiocarcinoma (CCA)
This study investigated the indirect mechanism through which HDAC6 affects pancreatic cancer
Summary
Gastrointestinal cancers involve various diseases, with many having poor prognoses. The incidences of colorectal and stomach cancers remains high; there are considerable mortality rates of cancer in the esophagus, liver, pancreas, stomach, and colon (Ferlay et al, 2019). There have been recent reports of the importance of histone deacetylase (HDAC)–mediated epigenetic process in the carcinogenesis (Schizas et al, 2020; Souza and Chatterji, 2015) This posttranslational modification is reversible; it has significant effects on chromatin structure/function and regulation of eukaryotic gene expression (Sanaei and Kavoosi, 2019). HDAC6 plays important role in ubiquitin proteosome system through proteosomal degradation of HSP90 (Matthias et al, 2008; Boyault et al, 2007b) (Figures 2A,B) It regulates cell migration, invasion, adhesion, and microtubule and skeletal dynamics through deacetylation of tubulin and cortactin (Miyake et al, 2016; Zhang et al, 2003) (Figure 2C). We briefly summarized recent studies on the inhibitors of HDAC6 in these cancers, which suggests that this versatile enzyme is an attractive therapeutic target
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