TTK: A Promising Target in Malignant Tumors

TTK, also known as MPS1 (the monopolar spindle 1)/ MPS1L1, is located on chromosome 6q13-q21 and encodes a dual-specific protein kinase that phosphorylates serine and threonine [1]. The spindle assembly checkpoint (SAC) plays a key role in mitosis. The SAC acts as a molecular monitoring mechanism, which delays mitosis until all chromosomes are properly attached to the spindle microtubules. As a key regulator of the SAC, TTK plays an important role in controlling cell cycle progression and maintaining genomic integrity [2]. TTK is vital for the recruitment of kinetochore components to unattached kinetochores and is essential for correcting improperly attached chromosomes. Interestingly, TTK is highly expressed in many types of malignant tumors [3]. However, TTK expression is low in most organs, except in the testis and placenta. Once TTK is inhibited, cancer cells exit mitosis prematurely, with more chromosome segregation errors and aneuploids. After several rounds of cell division, the accumulation of chromosome segregation errors may lead to cancer cell death [4]. Therefore, TTK has gradually become a research hotspot for anticancer drugs, and TTK inhibitors are increasingly being investigated in clinical trials.