Commitment of Scaffold Proteins in the Onco-Biology of Human Colorectal Cancer and Liver Metastases after Oxaliplatin-Based Chemotherapy.

Deborah Rotoli,Julio Ávila,María García,Ali Mobasheri,Manuel Morales,María Maeso,Pablo Martín-Vasallo

doi:10.3390/ijms18040891

Abstract

Scaffold proteins play pivotal roles in the regulation of signaling pathways, integrating external and internal stimuli to various cellular outputs. We report the pattern of cellular and subcellular expression of scaffoldins angiomotin-like 2 (AmotL2), FK506 binding protein 5 (FKBP51) and IQ motif containing GTPase-activating protein 1 (IQGAP1) in colorectal cancer (CRC) and metastases in liver resected after oxaliplatin-based chemotherapy (CT). Positive immunostaining for the three scaffoldins was found in most cells in healthy colon, tumor, healthy liver and metastasized liver. The patterns of expression of AmotL2, FKBP51 and IQGAP1 show the greatest variability in immune system cells and neurons and glia cells and the least in blood vessel cells. The simultaneous subcellular localization in tumor cells and other cell types within the tumor suggest an involvement of these three scaffoldins in cancer biology, including a role in Epithelial Mesenchymal Transition. The display in differential localization and quantitative expression of AmotL2, FKBP51, and IQGAP1 could be used as biomarkers for more accurate tumor staging and as potential targets for anti-cancer therapeutics by blocking or slowing down their interconnecting functions. Tough further research needs to be done in order to improve these assessments.

Highlights

Scaffold proteins bring together and facilitate macromolecular interactions between multiple modular partners that are committed to a specific subcellular task, usually forming a stable complex in a peculiar subcellular localization
We identified CD34+ telocytes (Figure 6N–Q and Figure S2I–P) and CD31+ stromal cells co-expressing IQ motif containing GTPase-activating protein 1 (IQGAP1) (Figure 6R–U, arrows)
Cellularity of colorectal cancer (CRC) consists of tumor cells, vascular endothelial cells and inflammatory immune cells infiltrating apparent normal colon tissue formed by mucosa, glandular, cryptal, submucosa and muscularis mucosa cells, interstitial cells, endothelial, pericytes and muscular cells of vessels and nerve cells of myenteric plexuses

Summary

Introduction

Scaffold proteins bring together and facilitate macromolecular interactions between multiple modular partners that are committed to a specific subcellular task, usually forming a stable complex in a peculiar subcellular localization. Colorectal cancer (CRC) is the fourth leading cause of cancer-associated mortality, and >95% of CRCs are adenocarcinomas [4,5]. In the search for early markers of oxaliplatin-related toxicity, we studied the differential transcriptomics in peripheral white cells (PWCs) from patients receiving oxaliplatin-based chemotherapy (CT) and found 502 genes significantly up- or down-regulated as a result of CT [9] Among those genes, some encoding scaffold proteins presented significant changes in their expression levels

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