Cellular apoptosis susceptibility (chromosome segragation 1-like, CSE1L) gene is a key regulator of apoptosis, migration and invasion in colorectal cancer

Ayham Alnabulsi, Abdelali Agouni, Suman Mitra, Isaac Garcia-Murillas, Brian Carpenter, Steve Bird, Graeme I Murray

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Cellular apoptosis susceptibility (chromosome segregation 1-like, CSE1L) gene maps to chromosomal region 20q13.13, a region frequently amplified in solid tumours. In this study, we investigated the roles played by CSE1L in colorectal cancer by examining CSE1L expression and clinico-pathological parameters in colorectal cancer and investigating the effect of CSE1L on the viability, adhesion and migration of colorectal cancer cells. RT-PCR showed that CSE1L mRNA was over-expressed in colorectal cancer. CSE1L depletion by knock down with CSE1L specific siRNA significantly reduced viability in HCT116 cells (p = 0.004) and SW480 cells (p = 0.003) whilst significantly increasing the proportion of apoptotic HCT116 cells (p<0.001) and SW480 cells (p<0.001). Furthermore, CSE1L depletion significantly reduced the adhesive capacity of HCT116 (p=0.003) and SW480 cells (p=0.004). Analysis by qRT-PCR following CSE1L siRNA treatment of HCT116 and SW480 cells showed significant modulation of key apoptotic (p53, p73 and BAK) and adhesive (E-cadherin, Ep-CAM and ICAM-1) molecules. Immunohistochemistry of a colorectal cancer tissue microarray showed that CSE1L had a significantly increased level in colorectal cancer compared to normal colorectal epithelium (p<0.001). There were significant decreases in both nuclear (p=0.006) and cytoplasmic (p=0.003) staining of CSE1L in tumours with lymph node metastasis (stage 3 tumours) compared with lymph node negative tumours (stage 1 and stage 2 tumours). In lymph node negative patients, poor survival was associated with increased CSE1L cytoplasmic expression (p=0.042). These results indicate that CSE1L is associated with viability and apoptosis, cellular adhesion and invasion, thus implicating CSE1L in the progression of colorectal cancer.
Original languageEnglish
Pages (from-to)471-481
Number of pages11
JournalThe Journal of pathology
Volume228
Issue number4
Early online date20 Aug 2012
DOIs
Publication statusPublished - Dec 2012

Keywords

  • adhesion
  • apoptosis
  • cellular apoptosis susceptibility gene
  • chromosome segregation 1-like protein CSE1L
  • colorectal cancer
  • migration
  • p53

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