LMP2 and TAP2 impair tumor growth and metastasis by inhibiting Wnt/β-catenin signaling pathway and EMT in cervical cancer

BMC Cancer. 2023 Nov 20;23(1):1128. doi: 10.1186/s12885-023-11639-y.

Abstract

Background: The roles of low molecular mass polypeptide 2 (LMP2) and transporter-associated with antigen processing (TAP2) in tumorigenesis are controversial. Here we aimed to explore the effect of LMP2 and TAP2 on the oncogenesis and metastasis of cervical cancer cells.

Methods: The expressions of LMP2 and TAP2 in cervical cancer and normal tissues were determined by qPCR. Plate colony formation, cell counting kit-8 analysis and in vivo tumor xenograft assays were used to detect the tumor growth. Wound healing and transwell assays were used to detect the metastasis of cervical cancer. Gelatin zymography and western blotting assays were used to detect the effect of LMP2 and TAP2 on the EMT and Wnt/β-catenin pathway in cervical cancer cells.

Results: In the present study, we reported that LMP2 and TAP2 levels were overexpressed in cervical cancer. Overexpression of LMP2 and TAP2 impaired the proliferation of Hela cells. In vivo studies substantiated that LMP2 and TAP2 antagonized tumor growth. Likewise, LMP2 and TAP2 overexpression decreased the migration and invasion ability of Hela cells by regulating the process of epithelial-mesenchymal transition (EMT). Mechanically, LMP2 and TAP2 subverted the protein abundance of Wnt1 and β-catenin, thereby downregulating their downstream targets Cyclin D1 and c-Myc. In addition, Wnt1 overexpression partially rescued the observed consequences of ectopic expression of LMP2 and TAP2 in cervical cancer cells. Taken together, our study revealed that LMP2 and TAP2 suppress the oncogenesis and metastasis of cervical cancer cells by Wnt/β-catenin pathway and altering EMT.

Conclusion: LMP2 and TAP2 may inhibit the oncogenesis and metastasis of cervical cancer cells by inhibiting the process of EMT and the Wnt/β-catenin signaling pathway, which may provide important insight into prospective targets for the treatment of cervical cancer.

Keywords: Cervical carcinoma; EMT; LMP2; Oncogenesis; TAP2; Wnt1.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 3 / metabolism
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Humans
  • Uterine Cervical Neoplasms* / genetics
  • Wnt Signaling Pathway
  • beta Catenin* / genetics
  • beta Catenin* / metabolism

Substances

  • beta Catenin
  • TAP2 protein, human
  • ATP Binding Cassette Transporter, Subfamily B, Member 3