Deciphering Mechanisms of Action of Sortilin/Neurotensin Receptor-3 in the Proliferation Regulation of Colorectal and Other Cancers

The purpose of this review is to decipher the mechanisms of the pathways leading to the complex roles of neurotensin (NTS) receptor-3, also called sortilin, and of its soluble counterpart (sSortilin/NTSR3) in a large amount of physiological and pathological functions, particularly in cancer progression and metastasis. Sortilin/NTSR3 belongs to the family of type I transmembrane proteins that can be shed to release its extracellular domain from all the cells expressing the protein. Since its discovery, extensive investigations into the role of both forms of Sortilin/NTSR3 (membrane-bound and soluble form) have demonstrated their involvement in many pathophysiological processes from cancer development to cardiovascular diseases, Alzheimer's disease, diabetes, and major depression. This review focuses particularly on the implication of membrane-bound and soluble Sortilin/NTSR3 in colorectal cancer tissues and cells depending on its ability to be associated either to neurotrophins (NTs) or to NTS receptors, as well as to other cellular components such as integrins. At the end of the review, some hypotheses are suggested to counteract the deleterious effects of these proteins in order to develop effective anti-cancer treatments.