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

Int J Mol Sci. 2017 Apr 22;18(4):891. 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.

Keywords: AmotL2; FKBP51; FOLFOX; IQGAP1; colorectal cancer; metastasized liver; oxaliplatin; pericytes; scaffold proteins; telocytes.

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Blood Vessels / metabolism
  • Blood Vessels / pathology
  • Carrier Proteins / metabolism
  • Colon / metabolism
  • Colon / pathology
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Epithelial-Mesenchymal Transition
  • Humans
  • Immunohistochemistry
  • Liver / metabolism
  • Liver / pathology
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary
  • Microscopy, Fluorescence
  • Organoplatinum Compounds / therapeutic use*
  • Oxaliplatin
  • Tacrolimus Binding Proteins / metabolism
  • ras GTPase-Activating Proteins / metabolism

Substances

  • AMOTL2 protein, human
  • Antineoplastic Agents
  • Carrier Proteins
  • IQ motif containing GTPase activating protein 1
  • Organoplatinum Compounds
  • ras GTPase-Activating Proteins
  • Oxaliplatin
  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 5