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TCF4 promotes colorectal cancer drug resistance and stemness via regulating ZEB1/ZEB2 expression

  • Shangfeng Sun
  • Xiuxiu Yang
  • Xingping Qin
  • Yuekun ZhaoEmail author
Original Article


The present study aims to investigate the roles of TCF4 and its underlying mechanism in colorectal cancer (CRC). Doxorubicin-resistant DLD-1 (DLD1 DR), TCF4 overexpression, and TCF4 knockdown cell lines were constructed. A flow cytometer was used to analyze frequencies of CD133+ cell in the DLD1 and DLD1 DR cells. Quantitative real-time PCR (qPCR) was used to determine the expressions of cancer stem cell (CSC) makers. Stemness of CRC cells were determined using tumorsphere formation assay. The correlation between TCF4 and ZEB1/ZEB2 were determined using public data from The Cancer Genome Atlas (TCGA) datasets. ZEB1/ZEB2 overexpression cell lines were constructed and cell viabilities were then determined using MTT and colony formation assays. TCF4 overexpression promoted proliferation of CRC cell lines and relative expressions of TCF4 were significantly increased in the DLD1 DR cells. TCF4 overexpression promoted CRC cell doxorubicin resistance, whereas TCF4 knockdown significantly decreased doxorubicin resistance. Additionally, TCF4 overexpression also significantly increased frequencies of CSC cells, expressions of CSC markers, and CRC ability to form tumorsphere. Furthermore, TCF4 promoted ZEB1 and ZEB2 expression, leading to CRC proliferation and doxorubicin resistance. TCF4 promoted CRC doxorubicin resistance and stemness by regulating expressions of ZEB1 and ZEB2.


Colorectal cancer Cancer stem cells TCF4 ZEB1 ZEB2 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Informed consent

Not applicable.


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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2020

Authors and Affiliations

  • Shangfeng Sun
    • 1
  • Xiuxiu Yang
    • 2
  • Xingping Qin
    • 3
  • Yuekun Zhao
    • 3
    Email author
  1. 1.Department of Colorectal Anal SurgeryThe Central Hospital of Zaozhuang Mining Group of ShandongZaozhuangChina
  2. 2.Department of Clinical LaboratoryThe Central Hospital of Zaozhuang Mining Group of ShandongZaozhuangChina
  3. 3.Department of GastroenterologyZaozhuang Municipal Hospital of Traditional Chinese MedicineZaozhuangChina

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