Scaffold Proteins in Gastrointestinal Tumors as a Shortcut to Oncoprotein Activation

Abstract

Background: The development of cancer involves uncontrolled cell proliferation, and multiple signaling pathways that regulate cell proliferation have been found to be dysregulated in cancers. Extracellular signal-regulated protein kinase (ERK) is one of three major subtypes in the mitogen-activated protein kinase (MAPK) families. The MAPK/ERK pathway (RAS/RAF1/MEK/ERK) plays an important part in promoting cell proliferation in response to growth factors, thereby serving as a driving signal in gastrointestinal (GI) tumors. In contrast, the p53 tumor suppressor functions as a “guardian of the genome” and stops cell proliferation when oncogenic signaling is activated. Summary: Both pathways constrain each other in healthy GI epithelium, facilitating controlled proliferation that is essential for tissue repair and regeneration. However, in GI tumors, the MAPK/ERK and p53 pathways are commonly dysregulated, in part due to abnormal posttranslational modifications. Hyperphosphorylation of the ERK protein causes sustained activation of cell proliferation, whereas hypoacetylation of the p53 protein impairs its transcriptional function and blocks cell apoptosis. Multiple scaffold proteins have been found to regulate the posttranslational modifications of ERK and p53 proteins in GI tumors. Key Message: Abnormal expression of scaffold proteins may contribute to the dysregulation of the MAPK and p53 signaling pathways and thereby contribute to the development of GI tumors. Practical Implications: Scaffold proteins are potential biomarkers and therapeutic targets in GI tumors.

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

“…With their protein-protein interaction modules, scaffold proteins assist the assembly of intracellular signaling complexes downstream of numerous receptors [ 3 ]. Abnormal expression of scaffold proteins may contribute to the dysregulation of signaling pathways and favor the development of tumors [ 4 , 5 ].…”