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International Journal of Oncology
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Article

Epithelial-mesenchymal transition and cancer stem cell-like phenotype induced by Twist1 contribute to acquired resistance to irinotecan in colon cancer

  • Authors:
    • Yong Yang
    • Guoxin Wang
    • Dajian Zhu
    • Yanfeng Huang
    • Yong Luo
    • Pengfei Su
    • Xiaowu Chen
    • Qian Wang
  • View Affiliations / Copyright

    Affiliations: Department of Gastrointestinal Surgery, Shunde First People's Hospital Affiliated to Southern Medical University, Shunde, Guangdong 528300, P.R. China, Department of Gastrointestinal Surgery, Shunde Women and Children's Hospital Affiliated to Jinan University, Shunde, Guangdong 528300, P.R. China, Department of Traditional Chinese Medicine, Shunde First People's Hospital Affiliated to Southern Medical University, Shunde, Guangdong 528300, P.R. China, Department of Hepatobiliary Surgery, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China
  • Pages: 515-524
    |
    Published online on: June 14, 2017
       https://doi.org/10.3892/ijo.2017.4044
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Abstract

Inherent and acquired chemoresistance reduce the effectiveness of irinotecan in the treatment of metastatic colorectal cancer (CRC). However, the molecular mechanisms underlying this resistance process are still unclear. Twist1 is one of the master transcription factors of epithelial-mesenchymal transition (EMT). Our previous study indicated that Twist1 is overexpressed in colon cancer tissues, and demonstrated that Twist1 plays a crucial role in the chemoresistance of CRC. In the present study, we further investigated how Twist1 contribute to acquired resistance to irinotecan in colon cancer. The irinotecan-resistant cells were established by gradual adaptation of increasing irinotecan concentrations in LoVo cells, named LoVo/CPT-11R cells. Results showed that cell viabilities to different anticancer drugs were markedly increased in LoVo/CPT-11R cells compared to LoVo cells. Moreover, LoVo/CPT-11R cells displayed EMT, CSC-like cellular morphology and relative biomarkers were also significantly increased. In addition, overexpressed Twist1 LoVo cells were established by lentivirus transfection assay, named LoVo/Twist1 cells. Results showed that the LoVo/Twist1 cells perform a distinctly decreased sensitivity to irinotecan, downregulated expression of E-cadherin, upregulated expression of cluster of differentiation 44 (CD44), and a significant enhancement of invasion and migration potential by regulation of MMP2 compared with control cells. In contrast, the inhibition of Twist1 transfected with siRNA could enhance the irinotecan sensitivity in LoVo/CPT-11R cells and downregulate the expression of vimentin and CD44. Our data provide evidence that EMT and CSC-like phenotype induced by Twist1 contribute to acquire resistance to irinotecan and enhanced migration and invasion in colon cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Yang Y, Wang G, Zhu D, Huang Y, Luo Y, Su P, Chen X and Wang Q: Epithelial-mesenchymal transition and cancer stem cell-like phenotype induced by Twist1 contribute to acquired resistance to irinotecan in colon cancer. Int J Oncol 51: 515-524, 2017.
APA
Yang, Y., Wang, G., Zhu, D., Huang, Y., Luo, Y., Su, P. ... Wang, Q. (2017). Epithelial-mesenchymal transition and cancer stem cell-like phenotype induced by Twist1 contribute to acquired resistance to irinotecan in colon cancer. International Journal of Oncology, 51, 515-524. https://doi.org/10.3892/ijo.2017.4044
MLA
Yang, Y., Wang, G., Zhu, D., Huang, Y., Luo, Y., Su, P., Chen, X., Wang, Q."Epithelial-mesenchymal transition and cancer stem cell-like phenotype induced by Twist1 contribute to acquired resistance to irinotecan in colon cancer". International Journal of Oncology 51.2 (2017): 515-524.
Chicago
Yang, Y., Wang, G., Zhu, D., Huang, Y., Luo, Y., Su, P., Chen, X., Wang, Q."Epithelial-mesenchymal transition and cancer stem cell-like phenotype induced by Twist1 contribute to acquired resistance to irinotecan in colon cancer". International Journal of Oncology 51, no. 2 (2017): 515-524. https://doi.org/10.3892/ijo.2017.4044
Copy and paste a formatted citation
x
Spandidos Publications style
Yang Y, Wang G, Zhu D, Huang Y, Luo Y, Su P, Chen X and Wang Q: Epithelial-mesenchymal transition and cancer stem cell-like phenotype induced by Twist1 contribute to acquired resistance to irinotecan in colon cancer. Int J Oncol 51: 515-524, 2017.
APA
Yang, Y., Wang, G., Zhu, D., Huang, Y., Luo, Y., Su, P. ... Wang, Q. (2017). Epithelial-mesenchymal transition and cancer stem cell-like phenotype induced by Twist1 contribute to acquired resistance to irinotecan in colon cancer. International Journal of Oncology, 51, 515-524. https://doi.org/10.3892/ijo.2017.4044
MLA
Yang, Y., Wang, G., Zhu, D., Huang, Y., Luo, Y., Su, P., Chen, X., Wang, Q."Epithelial-mesenchymal transition and cancer stem cell-like phenotype induced by Twist1 contribute to acquired resistance to irinotecan in colon cancer". International Journal of Oncology 51.2 (2017): 515-524.
Chicago
Yang, Y., Wang, G., Zhu, D., Huang, Y., Luo, Y., Su, P., Chen, X., Wang, Q."Epithelial-mesenchymal transition and cancer stem cell-like phenotype induced by Twist1 contribute to acquired resistance to irinotecan in colon cancer". International Journal of Oncology 51, no. 2 (2017): 515-524. https://doi.org/10.3892/ijo.2017.4044
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