Spindle and kinetochore-associated complex subunit 3 (SKA3) promotes stem cell-like properties of hepatocellular carcinoma cells through activating Notch signaling pathway

Shuya Bai; Wei Chen; Mengli Zheng; Xiju Wang; Wang Peng; Yuchong Zhao; Yun Wang; Si Xiong; Bin Cheng

doi:10.21037/atm-21-1572

Spindle and kinetochore-associated complex subunit 3 (SKA3) promotes stem cell-like properties of hepatocellular carcinoma cells through activating Notch signaling pathway

Ann Transl Med. 2021 Sep;9(17):1361. doi: 10.21037/atm-21-1572.

Authors

Shuya Bai¹, Wei Chen¹, Mengli Zheng¹, Xiju Wang^{1

2}, Wang Peng¹, Yuchong Zhao¹, Yun Wang¹, Si Xiong¹, Bin Cheng¹

Affiliations

¹ Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Digestive Endoscopy, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.

Abstract

Background: Cancer stemness contributes to hepatocellular carcinoma (HCC) initiation, metastasis, drug resistance, and recurrence. The spindle and kinetochore-associated (SKA) complex has been shown to be involved in tumor progression; however, its effects on cancer stem cell-like properties have not yet been examined. This research sought to study each subunit of the SKA complex in HCC systematically.

Methods: Bioinformatic analyses were carried out to examine the expression and clinical data of the SKA complex's each subunit in HCC. The expression of the target genes was detected by quantitative reverse transcription-polymerase chain reaction and Western blot assays. Clone formation and Transwell assays were performed to assess the proliferation and migration abilities of the SKA complex's each subunit. Sphere formation assays and subcutaneous xenograft experiments were performed to investigate the effects of SKA complex subunit 3 (SKA3) on the self-renewal and tumorigenic abilities of HCC.

Results: Each subunit of the SKA complex was highly expressed in HCC, but only SKA complex subunit 1 (SKA1) and SKA3 were associated with the poor overall survival of HCC patients. Additionally, the HCC cells overexpressing SKA3 exhibited increased migration, invasion, proliferation, self-renewal, Sorafenib resistance and tumorigenic abilities. Notch signaling played a vital role in the process by which SKA3 promoted HCC stemness.

Conclusions: SKA3 promotes HCC stem cell-like properties via the Notch signaling pathway. As SKA3 appears to act as a regulator of stemness in HCC, it might be a potential molecular target for HCC.

Keywords: Hepatocellular carcinoma (HCC); Notch signaling pathway; spindle and kinetochore-associated complex (SKA complex); spindle and kinetochore-associated complex subunit 3 (SKA3); stem cell-like properties.