Kinesin-like protein KIFC1 (KIFC1) (KIFC1)

Kinesin-like protein KIFC1 (KIFC1), also known as HSET, is a minus-end-directed microtubule motor protein belonging to the kinesin-14 family (UniProt Q9BW19). Its primary biological role involves cross-linking and sliding microtubules to facilitate the assembly and maintenance of the mitotic spindle during cell division. In many cancer cells, centrosome amplification occurs, which would typically lead to multipolar mitosis and cell death; however, KIFC1 enables these cells to survive by clustering extra centrosomes into two functional poles (Godinho & Pellman, Nature, 2014). Because KIFC1 is essential for the survival of cells with extra centrosomes but largely redundant in normal cells with two centrosomes, it is a promising target for selective cancer therapy. Pharmacological inhibition of KIFC1, using small molecules like AZ82 or CW069, disrupts this clustering mechanism, forcing cancer cells into lethal multipolar divisions while sparing healthy tissue (Wu et al., J Med Chem, 2013; Yang et al., Expert Opin Ther Targets, 2014). This selectivity makes KIFC1 an attractive target for treating high-grade tumors with significant centrosome amplification, such as triple-negative breast cancer and ovarian cancer.

Other names

HSETKinesin family member C1KNSL2Kinesin-related protein HSET

Inhibition of the kinesin motor's ATPase activity or microtubule binding, preventing the clustering of supernumerary centrosomes and inducing multipolar spindle formation and mitotic catastrophe (Pannu et al., Sci Rep, 2015; Wu et al., J Med Chem, 2013).