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

• Published in: The Journal of pathology Vol. 228; no. 4; pp. 471 - 481
• Main Authors: Alnabulsi, Ayham, Agouni, Abdelali, Mitra, Suman, Garcia-Murillas, Isaac, Carpenter, Brian, Bird, Steve, Murray, Graeme I
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.12.2012; Wiley; Wiley Subscription Services, Inc
• Subjects: adhesion; Adult; Aged; Aged, 80 and over; apoptosis; Apoptosis - genetics; Biological and medical sciences; Cell Movement - genetics; Cell Survival - genetics; cellular apoptosis susceptibility gene; Cellular Apoptosis Susceptibility Protein - genetics; chromosome segregation 1-like protein CSE1L; colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; HCT116 Cells; Humans; invasion; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Middle Aged; migration; Neoplasm Invasiveness - genetics; p53; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; RNA, Small Interfering - genetics; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Rectal disease; cellular apoptosis susceptibility gene; Colorectal cancer; Tumorous infiltration; Metastasis; Regulator; Genetic determinism; p53; TP53 Gene; Predisposition; Exportin 2; Intestinal disease; Genetics; Cell; Tumor suppressor gene; Malignant tumor; Adhesion; Chromosome 1; Invasion; Colonic disease; chromosome segregation 1-like protein CSE1L; Disjunction; Sensitivity; Cell death; migration; Digestive diseases; Cell migration; Cancer; Apoptosis; colorectal cancer; invasion; apoptosis; adhesion
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.4031

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 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. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.