Three steps to cancer: how phosphorylation of tubulin, tubulin tyrosine ligase and P-glycoprotein may generate and sustain cancer

Transformed cells progress to cancer because they are not eliminated by apoptosis. In this brief minireview I propose, based on published data, that the cell possesses a ‘last check point’ (LCP) apoptotic step in the form of assembly of nitrotyrosinated α-tubulin onto microtubules. This leads to microtubule dysfunction and ultimately apoptosis. I also propose that cells that escape this LCP apoptotic step develop into cancer. Phosphorylation of tubulin tyrosine ligase (TTL) is postulated to cause escape from LCP apoptosis. Phosphorylation also ensures that cancer cells survive a hostile milieu (e.g. chemotherapy).