TTK
Overview
TTK (TTK Protein Kinase), also known as MPS1, encodes a dual-specificity kinase essential for the spindle assembly checkpoint (SAC). It phosphorylates components of the kinetochore to ensure proper chromosome segregation. TTK is frequently overexpressed in high-grade cancers with chromosomal instability and is an active therapeutic target.
Alterations observed in the corpus
- Upregulated in the basal-like IntClust 10 subgroup of breast cancer as part of a chromosome 5q deletion-associated trans-acting mitotic network, alongside AURKB, BUB1, CHEK1, and FOXM1 PMID:22522925
Cancer types (linked)
- Breast cancer (basal-like, IntClust 10): transcriptional upregulation as part of a mitotic gene network associated with 5q deletion PMID:22522925
Co-occurrence and mutual exclusivity
- Upregulation co-occurs with AURKB, BUB1, CHEK1, and FOXM1 in IntClust 10 basal-like breast cancer PMID:22522925
Therapeutic relevance
- TTK kinase inhibitors are in active clinical development for chromosomally unstable cancers; the basal-like IntClust 10 subgroup with mitotic network upregulation may be a candidate for such agents.
Open questions
- Whether TTK upregulation in IntClust 10 is a direct consequence of 5q chromosomal loss or a separate transcriptional program is not fully resolved.
Sources
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