Spindle and kinetochore-associated protein 3 (SKA3) (SKA3)

Spindle and kinetochore-associated protein 3 (SKA3) is a critical component of the SKA complex, which is essential for stable kinetochore-microtubule attachment and proper chromosome segregation during mitosis [UniProt: Q8IXP3]. In many malignancies, SKA3 is significantly overexpressed and acts as an oncogene by promoting cell cycle progression and epithelial-mesenchymal transition [PMID: 31485245]. The SKA3-mediated PI3K/AKT/mTOR pathway refers to the signaling axis where SKA3 activates PI3K/AKT/mTOR to drive tumor proliferation, survival, and metastasis [PMID: 32853315]. While SKA3 itself is the primary molecular target, its regulation of this central pathway makes it a focal point for therapeutic development. Currently, there are no FDA-approved drugs targeting SKA3 directly, though experimental approaches using RNA interference have shown promise in preclinical models. Targeting this axis offers a strategy to induce mitotic catastrophe while simultaneously suppressing pro-survival signaling in cancer cells. As a mitotic regulator, SKA3 is also being investigated as a potential prognostic biomarker across various solid tumors [PMID: 30034190]. Its role in the spindle assembly checkpoint ensures that cells do not exit mitosis until chromosomes are correctly aligned, making its inhibition a potent trigger for apoptosis.

Other names

RAMA1C13orf3Spindle and kinetochore-associated complex subunit 3

Inhibition of SKA3 disrupts kinetochore-microtubule attachments leading to mitotic arrest and suppresses the activation of the PI3K/AKT/mTOR signaling pathway.