Functional Association between the Golgi and Microtubule Reorganisation in Cancer

Abstract

The microtubule organisation in cells depends on the microtubule nucleation sites and the microtubule dynamics. The microtubule dynamics are influenced by microtubule associated proteins (MAPs) and tubulin post-translational modifications (PTMs). The nucleation of microtubules from various microtubule organising centres (MTOCs) inside the cell is dictated by the presence of microtubule nucleating factors there. The centrosome nucleates most of the microtubules in the animal cell. Among the non-centrosomal microtubule organisers, the Golgi apparatus is the most studied. The microtubules originating from the Golgi have specific PTMs and are essential in intracellular transport and directional cell motility. The microtubule organisation in terms of its PTMs and interaction with MAPs changes in cancer compared to non-malignant cells. Microtubules in cancer cells share many characteristics of Golgi derived microtubules (GDMTs); therefore, GDMTs may be upregulated in these cancers. This study investigates whether the transcript levels of genes related to microtubule organisation, both at the centrosome and the Golgi, change in breast cancer. We see that centrosomal microtubule recruitment factors are transcriptionally upregulated in breast cancer, and many microtubule stabilisers specific to the Golgi are downregulated. We found that deregulation of some of these genes was also correlated with the aggressiveness of the breast cancer subtype of the patient and patient survival. Experiments in isogenic breast epithelial cell line series show upregulation of microtubule stability related PTMs in premalignant and malignant cell lines. The higher amount of nocodazole resistant microtubule in the malignant cell line than in the non-tumourigenic cell line supports the higher microtubule stability in the malignant cell line.