P-219 - The role of the putative tumor suppressor protein spinophilin in colorectal cancer

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Colon Cancer
Rectal Cancer
Translational Research
Presenter V. Stiegelbauer
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors V. Stiegelbauer1, A. Ress1, D. Schwarzenbacher1, A. Deutsch1, S. Perakis1, H. Ling1, C. Ivan2, G. Calin1, A. Gerger1, B. Rinner1, M. Pichler1
  • 1Medical University of Graz, Graz/AT
  • 2The University of Texas MD Anderson Cancer Center, Houston/US

Abstract

Introduction

In this study, we investigated the clinical and biological role of spinophilin in colorectal cancer patients and cell lines.

Methods

For the validation of the prognostic value of spinophilin we analysed the mRNA expression data of 162 colon adenocarcinoma patients. The biological role of spinophilin in colorectal cancer cells was further studied by knock-down experiments in colorectal cancer cell lines.

Results

Low spinophilin expression is significantly associated with poor prognosis in colorectal cancer patients. This clinical finding can be partly explained by increased cellular growth rates. At molecular level, a reduction of spinophilin levels increased the expression of the transcription factor E2F-1. Additionally, we observed an increased formation of tumor spheres, increased number of CD133 positive cells and a higher resistance to 5-flourouracil (p < 0.05).

Conclusion

In our study we confirmed the previously identified link between low spinophilin expression and poor prognosis in CRC patients. Additionally, we demonstrated that spinophilin might be involved in cancer stem cell formation. E2F-1 signalling is activated and seems to explain the higher cellular growth rates observed in spinophilin knock-down colorectal cancer cells.