Frontiers in Oncology (Jun 2021)

EMT and Cancer Cell Stemness Associated With Chemotherapeutic Resistance in Esophageal Cancer

  • Xiaojie Liu,
  • Xiaojie Liu,
  • Xiaojie Liu,
  • Mingjing He,
  • Mingjing He,
  • Mingjing He,
  • Linlin Li,
  • Linlin Li,
  • Linlin Li,
  • Xiya Wang,
  • Xiya Wang,
  • Xiya Wang,
  • Shuhua Han,
  • Shuhua Han,
  • Shuhua Han,
  • Jinzhu Zhao,
  • Jinzhu Zhao,
  • Jinzhu Zhao,
  • Yalong Dong,
  • Yalong Dong,
  • Yalong Dong,
  • Mushtaq Ahmad,
  • Mushtaq Ahmad,
  • Mushtaq Ahmad,
  • Leilei Li,
  • Leilei Li,
  • Leilei Li,
  • Xueyan Zhang,
  • Xueyan Zhang,
  • Xueyan Zhang,
  • Junfeng Huo,
  • Junfeng Huo,
  • Junfeng Huo,
  • Yunfan Liu,
  • Chengxue Pan,
  • Chengxue Pan,
  • Cong Wang,
  • Cong Wang,
  • Cong Wang

DOI
https://doi.org/10.3389/fonc.2021.672222
Journal volume & issue
Vol. 11

Abstract

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Drug resistance often occurs after chemotherapy in esophageal cancer patients, leading to cancer metastasis and recurrence. However, the relationship among cancer cell migration, recurrence and drug resistance in esophageal cancer drug-resistant cells has not been clearly explained. In this study, we constructed paclitaxel (PTX)-resistant esophageal cancer cells to explore the causes of drug resistance and poor prognosis after chemotherapy in esophageal cancer. Colony formation assay was used to evaluate the difference of colony formation between parental cells and drug resistance cells. Microsphere formation assay was used to examine the phenotype of stem cells. Wound healing and Transwell assays were used to detect the migration ability of drug-resistant cells. Western blotting and immunofluorescence assays were used to explore the mechanisms. Finally, we used nude mouse xenograft model to explore the tumor characteristics and the expression of relative proteins to verify our findings in vivo. Our study demonstrated that the cancer cell stemness characteristics exist in drug-resistant esophageal cancer cells, that expressed the biomarkers of stem cells and were prone to epithelial-mesenchymal transition (EMT). Our results suggested that the expression of EMT biomarkers and stemness-related proteins increased in esophageal cancer cells after continuously using chemotherapeutic drugs for a period of time. This study indicated that simultaneously targeting EMT and stemness could be a better strategy for the treatment of esophageal cancer drug resistance.

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