NCAPD2 inhibits autophagy by regulating Ca2+/CAMKK2/AMPK/mTORC1 pathway and PARP-1/SIRT1 axis to promote colorectal cancer. (1st November 2021)

• Record Type: Journal Article
• Authors: Jing, Zuolei; He, Xinyuan; Jia, Zhirong; Sa, Yunli; Yang, Bolin; Liu, Ping
• Is Part Of: Cancer letters. Volume 520(2021)
• Page Start: 26
• Page End: 37
• Publication Date: 2021-11-01
• Subjects: Colorectal cancer -- NCAPD2 -- Autophagy -- PARP-1/SIRT1 -- CAMKK/AMPK pathway; CRC colorectal cancer -- NCAPD2 Non-SMC condensin I complex subunit D2 (NCAPD2) -- AOM azoxymethane -- DSS dextran sulfate sodium -- qRT-PCR quantitative real-time PCR -- IHC immunohistochemistry -- CAMKK2 Ca2+/calmodulin dependent kinase type β -- AMPK AMP-activated kinase -- PAR poly(ADP-ribose) polymers; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2021.06.029
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Non-SMC condensin I complex subunit D2 (NCAPD2) is one of the three non-SMC subunits in condensin I. Previous studies have shown that NCAPD2 plays an important role in the chromosome condensation and segregation. However, its role in the development of colorectal cancer (CRC) and specific molecular mechanisms still need to be further studied. Here we show that NCAPD2 inhibits autophagy and blocks autophagic flux via Ca 2+ /CAMKK/AMPK/mTORC1 pathway and PARP-1/SIRT1 axis. NCAPD2 acts as a tumor promoter both in vitro and in vivo. NCAPD2 knockout suppresses colorectal cancer development in AOM/DSS induced mice model. Therefore, our findings support a role for NCAPD2 in autophagy to promote CRC development and highlight NCAPD2 as a potential target for CRC therapy. Highlights: NCAPD2 is high expression and promotes cancer progression in CRC. NCAPD2 plays an important role in both the occurrence and development of colorectal cancer. Both Ca 2+ /CAMKK/AMPK/mTORC1 pathway and PARP-1/SIRT1 axis involves in the functions of NCAPD2 in CRC.