Knockdown of XB130 restrains cancer stem cell-like phenotype through inhibition of Wnt/β-Catenin signaling in breast cancer

Mol Carcinog. 2019 Oct;58(10):1832-1845. doi: 10.1002/mc.23071. Epub 2019 Jun 20.

Abstract

The cancer stem cells (CSCs) is a subset of cancer cells that possess stem cell properties, which plays a crucial role in the occurrence, metastasis, and recurrence of the tumor. XB130 is a novel adapter protein potentially serves as a functional factor in CSCs. To determine the role of CSCs in breast cancer, we focused on the study of XB130. In our study, we found that XB130 expression was significantly upregulated in breast cancer and was closely related to the clinicopathologic characteristics, overall survival and poor prognosis of breast cancer patients. Functionally, we found that knockdown of XB130 was not only played an important role in proliferation, epithelial-mesenchymal transition (EMT), and metastasis in breast cancer cells but also exhibited potent antitumor activity in animal tumor models. Moreover, we demonstrated that silencing endogenous XB130 regulated the cancer stem cell-like properties of breast cancer, including the formation of self-renewing spheres and the proportion of breast cancer SP+ cells. Mechanistically, our studies indicated that downregulation of XB130 restrained the EMT and Wnt/β-catenin signaling, so as to weaken the tumor-initiating cell-like phenotype of breast cancer cells. This study indicates that XB130 plays an important role in maintaining the EMT and stem cell-like characteristics of breast cancer cells, supporting the significance of XB130 as a new potential therapeutic target for early diagnosis and prognosis of breast cancer.

Keywords: EMT; SP+ cells; cancer stem cells; mammosphere.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Animals
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Heterografts
  • Humans
  • Mice
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Prognosis
  • Wnt Signaling Pathway / genetics

Substances

  • AFAP1L2 protein, human
  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor