TGIF1 plays a carcinogenic role in esophageal squamous cell carcinoma through the Wnt/β‑catenin and Akt/mTOR signaling pathways

Int J Mol Med. 2021 May;47(5):77. doi: 10.3892/ijmm.2021.4910. Epub 2021 Mar 11.

Abstract

TGFB induced factor homeobox 1 (TGIF1), a transcriptional corepressor, has been reported to be involved in tumorigenesis and cancer development. However, the role of TGIF1 in the growth and metastasis of esophageal cancer is poorly studied. In the present study, it was found that TGIF1 was highly expressed in esophageal cancer tissues and cell lines. The silencing of TGIF1 by siRNA interference significantly inhibited the proliferation, migration, invasion and epithelial‑mesenchymal transition (EMT) process of KYSE‑150 esophageal cancer cells, and promoted cell apoptosis. Correspondingly, the upregulation of TGIF1 significantly promoted the proliferation and metastatic potential of Eca‑109 cells, and reduced apoptosis. Furthermore, the data indicated that the Wnt/β‑catenin and Akt/mammalian target of rapamycin (mTOR) signaling pathways were inhibited by TGIF1 knockdown, and were promoted by the overexpression of TGIF1. It was also confirmed that TGIF1 knockdown reduced tumor growth, inhibited Wnt/β‑catenin and Akt/mTOR pathway activation, and reversed the TGF‑β1‑mediated EMT process in a tumor xenograft model. Taken together, the data of the present study suggest that TGIF1 plays an oncogenic role in the progression of esophageal cancer. It may carry out this role by regulating the Wnt/β‑catenin and Akt/mTOR signaling pathways.

Keywords: esophageal cancer; TGFB induced factor homeobox 1; proliferation; invasion; Wnt/β‑catenin; Akt/mammalian target of rapamycin.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology*
  • Esophageal Squamous Cell Carcinoma / metabolism
  • Esophageal Squamous Cell Carcinoma / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Mice
  • Mice, Nude
  • Proto-Oncogene Proteins c-akt / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • TOR Serine-Threonine Kinases / metabolism
  • Wnt Signaling Pathway
  • Xenograft Model Antitumor Assays

Substances

  • Homeodomain Proteins
  • Repressor Proteins
  • TGIF1 protein, human
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases

Grants and funding

The present study was supported by grants from the Academic promotion program of Shandong First Medical University (no. 2020RC002), the National Natural Science Foundation of China (nos. 81530060, 81874224 and 81671785), the National Key Research and Development Program of China (no. 2016YFC0105106), the Key Research and Development Project of Shandong Provincial (no. 2016GSF201123), and the Foundation of Taishan Scholars (nos. ts20120505, tsqn201909187 and tsqn201909140).