Dysregulation of Microtubule Nucleating Proteins in Cancer Cells

Simple Summary: The dysfunction of microtubule nucleation in cancer cells changes the overall cytoskeleton organization and cellular physiology. This review focuses on the dysregulation of the gamma-tubulin ring complex (gamma-TuRC) proteins that are essential for microtubule nucleation. Recent research on the high-resolution structure of gamma-TuRC has brought new insight into the microtubule nucleation mechanism. We discuss the effect of gamma-TuRC protein overexpression on cancer cell behavior and new drugs directed to gamma-tubulin that may offer a viable alternative to microtubule-targeting agents currently used in cancer chemotherapy. In cells, microtubules typically nucleate from microtubule organizing centers, such as centrosomes. gamma-Tubulin, which forms multiprotein complexes, is essential for nucleation. The gamma-tubulin ring complex (gamma-TuRC) is an efficient microtubule nucleator that requires additional centrosomal proteins for its activation and targeting. Evidence suggests that there is a dysfunction of centrosomal microtubule nucleation in cancer cells. Despite decades of molecular analysis of gamma-TuRC and its interacting factors, the mechanisms of microtubule nucleation in normal and cancer cells remains obscure. Here, we review recent work on the high-resolution structure of gamma-TuRC, which brings new insight into the mechanism of microtubule nucleation. We discuss the effects of gamma-TuRC protein dysregulation on cancer cell behavior and new compounds targeting gamma-tubulin. Drugs inhibiting gamma-TuRC functions could represent an alternative to microtubule targeting agents in cancer chemotherapy.

Automated summary

The dysfunction of microtubule nucleation in cancer cells alters the cytoskeleton organization and cellular physiology, with a focus on dysregulation of the gamma-tubulin ring complex (gamma-TuRC) proteins. Recent research on the high-resolution structure of gamma-TuRC provides new insights into the mechanism of microtubule nucleation, potentially offering new drug targets for cancer chemotherapy.