CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Université Côte d'Azur, OK660 Route des Lucioles, 06560 Valbonne, France.
Int J Mol Sci. 2022 Oct 6;23(19):11888. doi: 10.3390/ijms231911888.
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.
本文旨在阐释神经降压素（NTS）受体-3（也称为分选连接蛋白）及其可溶性对应物（sSortilin/NTSR3）在大量生理和病理功能，特别是在癌症进展和转移中所扮演的复杂角色的途径机制。分选连接蛋白/NTSR3 属于 I 型跨膜蛋白家族，该家族蛋白可通过脱落作用从所有表达该蛋白的细胞中释放其细胞外结构域。自发现以来，大量研究表明，无论是膜结合形式还是可溶性形式的分选连接蛋白/NTSR3 都参与了许多病理生理过程，从癌症发展到心血管疾病、阿尔茨海默病、糖尿病和重度抑郁症等。本文特别关注膜结合型和可溶性型分选连接蛋白/NTSR3 在结直肠癌细胞和组织中的作用，这取决于其与神经营养因子（NTs）或 NTS 受体结合的能力，以及与整合素等其他细胞成分的结合能力。在本文的结尾，提出了一些假设，旨在对抗这些蛋白质的有害影响，从而开发有效的抗癌治疗方法。
