RT Journal Article
SR Electronic
T1 Blockade of GRP78 Translocation to the Cell Surface by HDAC6 Inhibition Suppresses Proliferation of Cholangiocarcinoma Cells
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 471
OP 482
DO 10.21873/anticanres.15505
VO 42
IS 1
A1 CHORONG KIM
A1 SEONMIN LEE
A1 DANBEE KIM
A1 DA SOL LEE
A1 EUNJUNG LEE
A1 CHANGHOON YOO
A1 KYU-PYO KIM
YR 2022
UL http://ar.iiarjournals.org/content/42/1/471.abstract
AB Background/Aim: HDAC6, a cytoplasmic localized deacetylase, is a positive regulator of cancer progression via modification of various substrates. We evaluated how the interaction between HDAC6 and glucose regulatory protein 78 (GRP78) affects the growth of cholangiocarcinoma (CCA). Materials and Methods: The anti-tumor effects of ACY-1215, an HDAC6 specific inhibitor, in CCA cell lines were analyzed by cell viability assay, western blotting, flow cytometry, co-immunoprecipitation, and biotinylation assays. In vivo effects of ACY-1215 were evaluated in a xenograft model using CCA cell line TFK-1. Results: ACY-1215 increased the acetyl-form of GRP78 by approximately 50% compared to control, which impaired the translocation of GRP78 to the plasma membrane by 50% through alteration of cellular proliferative signaling via PI3K/AKT. Furthermore, ACY-1215 suppressed tumor growth by 50% compared to vehicle control in a CCA xenograft model. Conclusion: Increase in GRP78 acetylation by HDAC6 inhibition suppressed GRP78 translocation to the cell surface, which inhibited proliferation and promoted apoptosis in CCA.