Copyright ©The Author(s) 2018.
World J Gastroenterol. Nov 7, 2018; 24(41): 4635-4642
Published online Nov 7, 2018. doi: 10.3748/wjg.v24.i41.4635
Table 1 Histone deacetylase-associated mechanisms of action in carcinogenesis
Increased expression of genes associated with the cell cycle, increasing proliferation, by overpassing the G1-S checkpoint, either by increasing CDK-2 and -4[12], or by inhibiting p21 protein that arrests cell cycle[13].
Inhibition of both the intrinsic and extrinsic apoptotic pathways[15].
Acyl group removal from other non-histone proteins, like transcription factors and regulatory proteins, indirectly affecting cellular proliferation[8].
Increased macropinocytosis, a process closely related to cellular migration and increased metastatic potential[19].
Increased chemotherapy resistance in tumor cells[21].
Protection from cellular damage caused by ROS[22].
Inhibition of angiogenesis by decreasing VEGF and HIF-1α[22].
Reduction of E-cadherin and increased vimentin expression, increasing metastatic potential[12].
Increased HSP function, conferring stability to oncogenic proteins[33].
Decreased function of DNA repair enzymes[39].
Table 2 Studies on the association of histone deacetylase involvement in esophageal cancer
Ref.YearNumber of pathology samplesHDACs/HATs studiedCorrelation with clinicopathological data
Langer et al[29]2010180 EC samplesHDAC1 and 2Increased N stage and Tumor Grade correlated with increased HDAC2 expression
Xue et al[30]2014167 EC samplesHDAC1 and HAT1Increased Tumor Grade correlated with increased HAT1 expression
Zeng et al[12]201686 ESCC samplesHDAC4Increased T, N, M, TNM stage, Tumor Grade and increased metastatic potential correlated with increased HDAC4 expression Worse 5-yr OS and DFS was noted in patients with increased HDAC4 expression
Tao et al[33]2018Study performed on cell lines of ECHDAC6Increased cell motility and invasion capacity and increased HSP-90 activity, conferring oncogenic protein stability, correlated with increased HDAC6 expression