SPC25 promotes proliferation and stemness of hepatocellular carcinoma cells via the DNA-PK/AKT/Notch1 signaling pathway

Yang, Jieying; Huang, Yue; Song, Mengjia; Pan, Qiuzhong; Zhao, Jingjing; He, Junyi; Ouyang, Dijun; Yang, Chaopin; Han, Yulong; Tang, Yan; Wang, Qijing; He, Jia; Li, Yongqiang; Chen, Hao; Weng, Desheng; Xiang, Tong; Xia, JianChuan

doi:10.7150/ijbs.71694

Theranostics

International Journal of Medical Sciences

Nanotheranostics

Journal of Cancer

Journal of Genomics

open access Global reach, higher impact

Full Text | PDF

Int J Biol Sci 2022; 18(14):5241-5259. doi:10.7150/ijbs.71694 This issue Cite

Research Paper

SPC25 promotes proliferation and stemness of hepatocellular carcinoma cells via the DNA-PK/AKT/Notch1 signaling pathway

Jieying Yang^1,2*, Yue Huang^1,2*, Mengjia Song^1,2*, Qiuzhong Pan^1,2, Jingjing Zhao^1,2, Junyi He^1,2, Dijun Ouyang³, Chaopin Yang^1,2, Yulong Han^1,2, Yan Tang^1,2, Qijing Wang^1,2, Jia He^1,2, Yongqiang Li^1,2, Hao Chen^1,2, Desheng Weng^1,2, Tong Xiang^1,2✉, JianChuan Xia^1,2✉

1. Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
2. Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.
3. Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China.
*These authors contributed equally to this work.

✉ Corresponding authors: JianChuan Xia, PhD, MD, State Key Laboratory of Oncology in South China, Department of Biotherapy, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, P. R. China. Tel.: +86-20-87345699, Fax: +86-20 More

Citation:

Yang J, Huang Y, Song M, Pan Q, Zhao J, He J, Ouyang D, Yang C, Han Y, Tang Y, Wang Q, He J, Li Y, Chen H, Weng D, Xiang T, Xia J. SPC25 promotes proliferation and stemness of hepatocellular carcinoma cells via the DNA-PK/AKT/Notch1 signaling pathway. Int J Biol Sci 2022; 18(14):5241-5259. doi:10.7150/ijbs.71694. https://www.ijbs.com/v18p5241.htm

Other styles

Abstract

The imbalance of kinetochore-microtubule attachment during cell mitosis is a response to the initiation and progression of human cancers. Spindle component 25 (SPC25) is indispensable for spindle apparatus organization and chromosome segregation. SPC25 plays an important role in the development of malignant tumors, but its role in hepatocellular carcinoma (HCC) is yet to be determined. In this study, we aimed to preliminarily investigate the role of SPC25 in HCC progression and the molecular mechanisms underlying the process. We identified SPC25 as a clinically notable molecule significantly correlated with the grade of malignancy and poor survival in both The Cancer Genome Atlas (TCGA) cohort and the HCC patient cohort from our center. Mechanistically, SPC25 promoted the incidence of DNA damage and activated the DNA-PK/Akt/Notch1 signaling cascade in HCC cells; the NICD/ RBP-Jκ complex directly targeted SOX2 and NANOG in a transcriptional manner to regulate the proliferation and self-renewal of HCC cells. Our study suggests that HCC-intrinsic SPC25/DNA-PK/Akt/Notch1 signaling is an important mechanism to promote carcinogenesis by regulating the proliferation and stemness program, which provides possible biomarkers for predicting HCC progression and poor survival, as well as potential therapeutic targets for HCC patients.

Keywords: SPC25, hepatocellular carcinoma, stemness, DNA-PK/AKT, Notch1

Citation styles

APA

Yang, J., Huang, Y., Song, M., Pan, Q., Zhao, J., He, J., Ouyang, D., Yang, C., Han, Y., Tang, Y., Wang, Q., He, J., Li, Y., Chen, H., Weng, D., Xiang, T., Xia, J. (2022). SPC25 promotes proliferation and stemness of hepatocellular carcinoma cells via the DNA-PK/AKT/Notch1 signaling pathway. International Journal of Biological Sciences, 18(14), 5241-5259. https://doi.org/10.7150/ijbs.71694.

ACS

Yang, J.; Huang, Y.; Song, M.; Pan, Q.; Zhao, J.; He, J.; Ouyang, D.; Yang, C.; Han, Y.; Tang, Y.; Wang, Q.; He, J.; Li, Y.; Chen, H.; Weng, D.; Xiang, T.; Xia, J. SPC25 promotes proliferation and stemness of hepatocellular carcinoma cells via the DNA-PK/AKT/Notch1 signaling pathway. Int. J. Biol. Sci. 2022, 18 (14), 5241-5259. DOI: 10.7150/ijbs.71694.

NLM

CSE

Yang J, Huang Y, Song M, Pan Q, Zhao J, He J, Ouyang D, Yang C, Han Y, Tang Y, Wang Q, He J, Li Y, Chen H, Weng D, Xiang T, Xia J. 2022. SPC25 promotes proliferation and stemness of hepatocellular carcinoma cells via the DNA-PK/AKT/Notch1 signaling pathway. Int J Biol Sci. 18(14):5241-5259.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.