Involvement of the Inositol-trisphosphate Receptor in Invasive or Migratory-type Breast Cancers

Breast cancer is the leading cause of female cancer and female death by cancer in France. Despite the improvement in early detection and therapeutic arsenal, the mortality of this cancer remains high with 11 886 deaths estimated in 2012. Breast cancer is most often a carcinoma born from the lobular or ductal epithelium and is classified In two main categories: non invasive and invasive. Invasive breast cancers account for 75% of the cases. They are usually ductal (75%) and more rarely lobular (25%). The cancer cells are then no longer circumscribed to the galactophoric canals or glands but have invaded neighboring tissues. If they are not treated in time, these cancers can then spread: the cancerous cells will then migrate either by the lymphatic vessels to reach the neighboring ganglia or through the blood vessels to give metastases in other tissues In the liver, lungs and bones). The mortality associated with breast cancer is not due to the growth of the primary tumor but rather to the occurrence of metastases. The study of the mechanisms leading to metastatic invasion (i.e. migration and invasion) is therefore of considerable importance. The development of metastases depends on the acquisition by the cancer cells of various capacities including that of being able to migrate, involving a remodeling of the cytoskeleton highly dependent on the intracellular calcium (Ca2 +) concentration. Several types of signals are able to induce mobilization of Ca2 + from the extracellular medium or endoplasmic reticulum (ER) reserves. At the intracellular level, some of these signals are generated by inositol (1,4,5) -trisphosphate (IP3) from the activation of G protein-coupled receptors or certain receptors with tyrosine kinase activity. Has been shown that the expression, activity and regulation of IP3R receptors (IP3Rs) are involved in the cancerous processes of many tissues, in particular in the phenomena of proliferation of breast cancer cells. Overall, altered expression an