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. 2021 Nov 1:520:26-37.
doi: 10.1016/j.canlet.2021.06.029. Epub 2021 Jul 3.

NCAPD2 inhibits autophagy by regulating Ca2+/CAMKK2/AMPK/mTORC1 pathway and PARP-1/SIRT1 axis to promote colorectal cancer

Zuolei Jing  1 , Xinyuan He  2 , Zhirong Jia  2 , Yunli Sa  2 , Bolin Yang  3 , Ping Liu  4
Affiliations

NCAPD2 inhibits autophagy by regulating Ca2+/CAMKK2/AMPK/mTORC1 pathway and PARP-1/SIRT1 axis to promote colorectal cancer

Zuolei Jing et al. Cancer Lett. .

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 Ca2+/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.

Keywords: Autophagy; CAMKK/AMPK pathway; Colorectal cancer; NCAPD2; PARP-1/SIRT1.

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