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

Zuolei Jing; Xinyuan He; Zhirong Jia; Yunli Sa; Bolin Yang; Ping Liu

doi:10.1016/j.canlet.2021.06.029

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

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

Authors

Zuolei Jing¹, Xinyuan He², Zhirong Jia², Yunli Sa², Bolin Yang³, Ping Liu⁴

Affiliations

¹ College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, People's Republic of China. Electronic address: Jingzuolei0212@163.com.
² College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, People's Republic of China.
³ Department of Colorectal Surgery, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
⁴ College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, People's Republic of China. Electronic address: liuping0805@njnu.edu.cn.

PMID: 34229059
DOI: 10.1016/j.canlet.2021.06.029

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

AMP-Activated Protein Kinase Kinases / genetics
Animals
Apoptosis / genetics
Autophagy / genetics
Calcium / metabolism
Calcium-Calmodulin-Dependent Protein Kinase Kinase / genetics*
Cell Line, Tumor
Chromosomal Proteins, Non-Histone / genetics*
Colorectal Neoplasms / genetics*
Colorectal Neoplasms / pathology
Humans
Mechanistic Target of Rapamycin Complex 1 / genetics
Mice
Mice, Knockout
Poly (ADP-Ribose) Polymerase-1 / genetics
Poly-ADP-Ribose Binding Proteins / genetics*
Signal Transduction / genetics
Sirtuin 1 / genetics

Substances

Chromosomal Proteins, Non-Histone
NCAPD2 protein, human
Ncapd2 protein, mouse
Poly-ADP-Ribose Binding Proteins
PARP1 protein, human
Poly (ADP-Ribose) Polymerase-1
Mechanistic Target of Rapamycin Complex 1
CAMKK2 protein, human
Calcium-Calmodulin-Dependent Protein Kinase Kinase
Camkk2 protein, mouse
AMP-Activated Protein Kinase Kinases
SIRT1 protein, human
Sirt1 protein, mouse
Sirtuin 1
Calcium