Abstract 8: Identifying the role of KIF20A in stemness and metastasis in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is remarkable for its high recurrence and metastasis rate. According to the cancer stem cell (CSC) model, a small group of stem cells is capable of keeping self-renewal, initiating relapse and metastasis in tumors. However, the mechanism of CSCs in regulating HCC recurrence and metastasis awaits further investigation. We previously established an in vitro human hepatocyte differentiation model and defined four developmental stages: embryonic stem cell (ES), endoderm (EN), liver progenitor cell (LN) and premature hepatocyte (PH). Kinesin family member 20A (KIF20A) was found highly expressed in ES and EN stages while decreasing sharply in LP and PH stages. Besides, in an online GEO dataset, we regrouped single cells into the hepatocyte, stem-like HCC and HCC subclusters according to their expression profiles. KIF20A was spotted mostly in the stem-like HCC cluster with a low proportion, sharing the same expression pattern with CD133, suggesting its potential role in cancer stemness. Moreover, KIF20A expression was positively correlated with stemness markers CD133, Epcam, CK19, and MYCN in our clinical cDNA array. In the TCGA-LIHC dataset, KIF20A expressed higher in tumor tissues than normal counterparts, and related to shorter overall survival in patients. Functionally, KIF20A promoted cell proliferation, induced sorafenib resistance, increased sphere formation, and enhanced cell migration and invasion in vitro. In subcutaneous mouse models, liver orthotopic mouse models and hydrodynamic transfection mouse model of HCC, KIF20A fueled tumorigenicity and lung metastasis significantly. After mRNA sequencing of KIF20A knock-down cells, bioinformatic analysis suggested that KIF20A may modulate metastatic biological processes via the Hippo pathway. Western Bloting further confirmed the result of pathway changes in protein level. The underlying mechanism of how KIF20A interacts with Hippo pathway still needs further investigation. In conclusion, we provided new insights into the role of KIF20A in regulating stemness and metastasis in HCC. KIF20A might be a potential target for HCC treatment in the future. Citation Format: Liuxian Ban, Xiaona Fang, Shan Liu, Jie Luo, Lanqi Gong, Hongyu Zhou, Beilei Liu, Jiao Huang, Nanzhou Yu, Yingchen Lyu, Licheng Tan, Qin Liu, Cuicui Huang, Xin-Yuan Guan. Identifying the role of KIF20A in stemness and metastasis in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 8.