Spindle and kinetochore-associated complex subunit 3 (SKA3)

Spindle and kinetochore-associated complex subunit 3 (SKA3) is a protein-coding gene encoding a 46.4 kDa protein that forms part of the trimeric SKA complex with SKA1 and SKA2. The SKA complex acts as a microtubule-binding subcomplex localized to the outer kinetochore, crucial for stable attachment of kinetochores to spindle microtubules during mitosis and correct chromosome segregation. SKA3 undergoes dynamic phosphorylation, with cyclin-dependent kinase 1 (CDK1) facilitating its recruitment to kinetochores via the Ndc80 complex, ensuring coordinated chromosome separation. SKA3 is overexpressed in multiple cancers, particularly hepatocellular carcinoma (HCC), where it plays oncogenic roles by promoting cell proliferation, migration, invasion, stemness (via Notch pathway), and drug resistance (notably Sorafenib). Its expression correlates with poor prognosis, advanced tumor grade, and immune cell infiltration. Given its clinical associations, SKA3 is defined as a therapeutic target and a biomarker candidate, with drugs such as Sorafenib, Sunitinib, Paclitaxel, Doxorubicin, Gemcitabine, and VX-680 showing interactions based on sensitivity profiling in high SKA3-expressing contexts. Targeting SKA3 remains challenging due to its fundamental roles in cell division and potential side effects.

Other names

SKA3C13orf3RAMA1MGC4832spindle and kinetochore-associated protein 3

Induction of cell cycle arrest and inhibition of SKA3 leads to suppressed cell proliferation, migration, invasion, and increased drug sensitivity (Sorafenib). Sorafenib resistance is associated with SKA3 overexpression, potentially via Notch signaling. Notch signaling pathway activation by SKA3 leads to stemness and drug resistance in cancer.