College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, People's Republic of China.
College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, People's Republic of China.
Cancer Lett. 2021 Nov 1;520:26-37. doi: 10.1016/j.canlet.2021.06.029. Epub 2021 Jul 3.
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/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.
非 SMC 凝聚素 I 复合物亚基 D2（NCAPD2）是凝聚素 I 中的三个非 SMC 亚基之一。先前的研究表明，NCAPD2 在染色体凝聚和分离中发挥重要作用。然而，其在结直肠癌（CRC）发展中的作用及其特定的分子机制仍需要进一步研究。在这里，我们表明 NCAPD2 通过 Ca/CAMKK/AMPK/mTORC1 途径和 PARP-1/SIRT1 轴抑制自噬并阻断自噬通量。NCAPD2 在体外和体内均作为肿瘤促进剂发挥作用。NCAPD2 敲除可抑制 AOM/DSS 诱导的小鼠模型中结直肠癌的发展。因此，我们的研究结果支持 NCAPD2 在促进 CRC 发展的自噬中的作用，并强调 NCAPD2 作为 CRC 治疗的潜在靶点。
