Suppression of Cellular Apoptosis Susceptibility (CSE1L) Inhibits Proliferation and Induces Apoptosis in Colorectal Cancer Cells

  • Zhu, Jin-Hui ;
  • Hong, De-Fei ;
  • Song, Yong-Mao ;
  • Sun, Li-Feng ;
  • Wang, Zhi-Fei ;
  • Wang, Jian-Wei
  • Published : 2013.02.28


The cellular apoptosis susceptibility (CSE1L) gene has been demonstrated to regulate multiple cellular mechanisms including the mitotic spindle check point as well as proliferation and apoptosis. However, the importance of CSE1L in human colon cancer is largely unknown. In the present study, we examined expression levels of CSE1L mRNA by semiquantitative RT-PCR. A lentivirus-mediated small interfering RNA (siRNA) was used to knock down CSE1L expression in the human colon cancer cell line RKO. Changes in CSE1L target gene expression were determined by RT-PCR. Cell proliferation was examined by a high content screening assay. In vitro tumorigenesis was measured by colony-formation assay. Cell cycle distribution and apoptosis were detected by flow cytometric analysis. We found CSE1L mRNA to be expressed in human colon cancer cells. Using a lentivirus based RNAi approach, CSE1L expression was significantly inhibited in RKO cells, causing cell cycle arrest in the G2/M and S phases and a delay in cell proliferation, as well as induction of apoptosis and an inhibition of colony growth capacity. Collectively, the results suggest that silencing of CSE1L may be a potential therapeutic approach for colon cancer.


CSE1L;colorectal cancer;apoptosis;proliferation


  1. Akiyama Y, Watkins N, Suzuki H, et al (2003). GATA-4 and GATA-5 transcription factor genes and potential downstream antitumor target genes are epigenetically silenced in colorectal and gastric cancer. Mol Cell Biol, 23, 8429.
  2. Behrens P, Brinkmann U, Fogt F, Wernert N, Wellmann A (2001). Implication of the proliferation and apoptosis associated CSE1L/CAS gene for breast cancer development. Anticancer Res, 21, 2413-7.
  3. Behrens P, Brinkmann U, Wellmann A (2003). CSE1L/CAS: its role in proliferation and apoptosis. Apoptosis, 8, 39-44.
  4. Bera TK, Bera J, Brinkmann U, Tessarollo L, Pastan I (2001). Cse1l is essential for early embryonic growth and development. Mol Cell Biol, 21, 7020-4.
  5. Brinkmann U, Brinkmann E, Bera TK, Wellmann A, Pastan I (1999). Tissue-Specific Alternative Splicing of the CSE1L/CAS (Cellular Apoptosis Susceptibility) Gene* 1. Genomics, 58, 41-9.
  6. Castanotto D, Rossi JJ (2009). The promises and pitfalls of RNA-interference-based therapeutics. Nature, 457, 426-33.
  7. Chintharlapalli S, Papineni S, Lei P, Pathi S, Safe S (2011). Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors. BMC Cancer, 11, 371.
  8. Eberhart CE, Coffey R, Radhika A, et al (1994). Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology, 107, 1183.
  9. Kim JG, Chae YS, Sohn SK, et al (2008). Vascular endothelial growth factor gene polymorphisms associated with prognosis for patients with colorectal cancer. Clin Cancer Res, 14, 62.
  10. Liao CF, Luo SF, Shen TY, et al (2008). CSE1L/CAS, a microtubule-associated protein, inhibits taxol (paclitaxel)-induced apoptosis but enhances cancer cell apoptosis induced by various chemotherapeutic drugs. BMB Rep, 41, 210-6.
  11. Liao CF, Luo SF, Li LT, et al (2008). CSE1L/CAS, the cellular apoptosis susceptibility protein, enhances invasion and metastasis but not proliferation of cancer cells. J Exp Clin Canc Res, 27, 15.
  12. Mulkeen AL, Silva T, Yoo PS, et al (2006). Short Interfering RNA-Mediated Gene Silencing of Vascular Endothelial Growth Factor: Effects on Cellular Proliferation in Colon Cancer Cells. Arch Surg, 141, 367-74.
  13. O'Brien CA, Pollett A, Gallinger S, Dick JE (2007). A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature, 445, 106-10.
  14. Pai SI, Lin YY, Macaes B, et al (2005). Prospects of RNA interference therapy for cancer. Gene Ther, 13, 464-77.
  15. Suzuki H, Watkins DN, Jair KW, et al (2004). Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat Genet, 36, 417-22.
  16. Tai CJ, Shen SC, Lee WR, et al (2010). Increased cellular apoptosis susceptibility (CSE1L/CAS) protein expression promotes protrusion extension and enhances migration of MCF-7 breast cancer cells. Exp Cell Res, 316, 2969-81.
  17. Tsao TY, Tsai CS, Tung JN, et al (2009a). Function of CSE1L/CAS in the secretion of HT-29 human colorectal cells and its expression in human colon. Mol Cell Biocheml, 327, 163-70.
  18. Tsao TY, Tsai CSS, Tung JN, et al (2009b). Function of CSE1L/CAS in the secretion of HT-29 human colorectal cells and its expression in human colon. Mol Cell Biocheml, 327, 163-70.
  19. Tung MC, Tsai CSS, Tung JN, et al (2009). Higher prevalence of secretory CSE1L/CAS in sera of patients with metastatic cancer. Cancer Epidem Biomar, 18, 1570.
  20. Wellmann A, Flemming P, Behrens P, et al (2001). High expression of the proliferation and apoptosis associated CSE1L/CAS gene in hepatitis and liver neoplasms: correlation with tumor progression. Int J Mol Med, 7, 489.
  21. Zhang S, Yang JH, Guo CK, Cai P (2007). Gene silencing of TKTL1 by RNAi inhibits cell proliferation in human hepatoma cells. Cancer Lett, 253, 108-14.

Cited by

  1. Lack of Relation of AKAP12 with p53 and Bcl-2 in Colorectal Carcinoma vol.15, pp.8, 2014,
  2. The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer Therapy vol.11, pp.10, 2016,
  3. Quantitative analysis of gene expression in fixed colorectal carcinoma samples as a method for biomarker validation vol.13, pp.6, 2016,
  4. CAS (CSE1L) signaling pathway in tumor progression and its potential as a biomarker and target for targeted therapy vol.37, pp.10, 2016,
  5. Targeting nuclear transporters in cancer: Diagnostic, prognostic and therapeutic potential vol.68, pp.4, 2016,
  6. Expression of CAS/CSE1L, the Cellular Apoptosis Susceptibility Protein, Correlates With Neoplastic Progression in Barrett’s Esophagus pp.1541-2016, 2016,
  7. CSE1L interaction with MSH6 promotes osteosarcoma progression and predicts poor patient survival vol.7, pp.1, 2017,
  8. CSE1L participates in regulating cell mitosis in human seminoma pp.09607722, 2018,
  9. Positive Caricature Transcriptomic Effects Associated with Broad Genomic Aberrations in Colorectal Cancer vol.8, pp.1, 2018,
  10. Roles of the CSE1L-mediated nuclear import pathway in epigenetic silencing vol.115, pp.17, 2018,


Supported by : Natural Science Foundation of China