Scaffold proteins of cancer signaling networks: The paradigm of FK506 binding protein 51 (FKBP51) supporting tumor intrinsic properties and immune escape

Abstract

Scaffold proteins are crucial regulators of signaling networks, and their abnormal expression may favor the development of tumors. Among the scaffold proteins, immunophilin covers a unique role as ‘protein-philin’ (Greek ‘philin’ = friend) that interacts with proteins to guide their proper assembly. The growing list of human syndromes associated with the immunophilin defect underscores the biological relevance of these proteins that are largely opportunistically exploited by cancer cells to support and enable the tumor’s intrinsic properties. Among the members of the immunophilin family, the FKBP5 gene was the only one identified to have a splicing variant. Cancer cells impose unique demands on the splicing machinery, thus acquiring a particular susceptibility to splicing inhibitors. This review article aims to overview the current knowledge of the FKBP5 gene functions in human cancer, illustrating how cancer cells exploit the scaffolding function of canonical FKBP51 to foster signaling networks that support their intrinsic tumor properties and the spliced FKBP51s to gain the capacity to evade the immune system.

Circular RNA circDDX17 suppression to gastric cancer progression via the sponging miR-1208/miR-1279/FKBP5 axis and encodes a novel circDDX17-63aa protein

“…FKBP5 had a low expression in GC cells and GC tissues in our study, which inhibited GC cell proliferation, migration, and EMT. FKBP5 participates in the NF-B, Akt, AMPK/mTOR, and TGF-/EMT signaling pathways, which are all signal transduction pathways 47 . The ERK protein is a crucial component of the MAPK pathway, which plays a signi cant role in the development of gastric cancer by controlling the cell cycle, migration, apoptosis, and proliferation.…”