1. Academic Validation
  2. IGF-1 promotes multiple myeloma progression through PI3K/Akt-mediated epithelial-mesenchymal transition

IGF-1 promotes multiple myeloma progression through PI3K/Akt-mediated epithelial-mesenchymal transition

  • Life Sci. 2020 May 15;249:117503. doi: 10.1016/j.lfs.2020.117503.
Yue Peng 1 Fangmei Li 1 Peihua Zhang 1 Xiaman Wang 1 Ying Shen 2 Yuandong Feng 2 Yachun Jia 1 Ru Zhang 1 Jinsong Hu 3 Aili He 4
Affiliations

Affiliations

  • 1 Xi'an Jiaotong University Health Science Center, Xi'An City, Shaanxi Province, China.
  • 2 The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'An City, Shaanxi Province, China.
  • 3 Xi'an Jiaotong University Health Science Center, Xi'An City, Shaanxi Province, China. Electronic address: jinsong.hu@xjtu.edu.cn.
  • 4 Xi'an Jiaotong University Health Science Center, Xi'An City, Shaanxi Province, China. Electronic address: heaili_2008@163.com.
Abstract

Aims: To investigate the role and mechanism of insulin-like growth factor 1(IGF-1)-mediated EMT on multiple myeloma (MM) growth and metastasis.

Materials and methods: The expression data from GEO datasets were utilized to explore the expression levels of IGF-1 and epithelial-mesenchymal transition (EMT) markers in MM. Western blotting and flow cytometry analysis were performed to detect the protein levels of EMT markers as well as key components of the PI3K/Akt pathway. Cell proliferation ability was assessed using colony formation assay and EdU incorporation assays. Transwell migration and invasion assays were performed to assess cell metastasis properties. Vimentin was knocked down by using electro-transfection with small interfering RNA (siRNA) to detect the effect of IGF-1-mediated EMT on MM cell growth and metastasis.

Key findings: First of all, the analysis of GEO database revealed that IGF-1 was excessively expressed and closely correlated with the expression of the EMT markers in MM patients. Furthermore, we demonstrated that IGF-1 enhanced the acquisition of mesenchymal features in a time-dependent manner. Additionally, in vitro studies revealed that IGF-1-mediated mesenchymal phenotype promoted MM migration, invasion and colony formation. Finally, the mechanism study showed PI3K/Akt signaling pathway was involved in the IGF-1-induced EMT in MM cells.

Significance: IGF-1-induced mesenchymal phenotype contributed to MM progression via the PI3K/Akt pathway regulation.

Keywords

Epithelial-mesenchymal transition; Insulin-like growth factor-1; Multiple myeloma.

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