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