Role of HDAC6 and Its Selective Inhibitors in Gastrointestinal Cancer

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.

Role of Selective Histone Deacetylase 6 Inhibitor ACY-1215 in Cancer and Other Human Diseases

“…By removing acetyl groups from ε-amino-lysine of proteins ( Gallinari et al, 2007 ), HDACs not only alter transcription, but also promote the establishment or elimination of other post-translational lysine modifications such as methylation and ubiquitination. Biological processes induced by HDACs have a significant impact on human health, and HDACs abnormalities have been documented to play a key role in many human diseases, including cancer, neurological diseases, inflammatory diseases, and heart diseases ( Seto and Yoshida, 2014 ; Zhou et al, 2021 ).…”

HDAC6-dependent deacetylation of TAK1 enhances sIL-6R release to promote macrophage M2 polarization in colon cancer

“…In the past few decades, HDAC6 has been recognized as an important member of the HDAC family because it contains two deacetylase catalytic domains and is mainly located in the cytoplasm [ 39 , 40 ]. HDAC6 targets a wide range of substrates and participates in various biological functions, especially tumorigenesis [ 41 ]. However, the substrates and mechanisms reported thus far are insufficient to explain the broad functions of HDAC6.…”

HDAC6-Dependent Deacetylation of TAK1 Enhances sIL-6R Release to Promote Macrophage M2 Polarization in Colon Cancer

“…In the past few decades, HDAC6 has been recognized as an important member of the HDAC family because it contains two deacetylase catalytic domains and is mainly located in the cytoplasm (39,40). HDAC6 targets a wide range of substrates and participates in various biological functions, especially tumorigenesis (41). However, the substrates and mechanisms reported thus far are insu cient to explain the broad functions of HDAC6.…”